Skip to main content

Cancer Biology: Some Causes for a Variety of Different Diseases

  • Chapter
  • First Online:
Cancer Targeted Drug Delivery

Abstract

Advances and integration of biochemistry, cell biology, molecular biology, and genetics have led to a better fundamental understanding of cancer biology and the causes for many types of cancer. Cancer is now thought to originate following either the “cancer stem cell hypothesis” or the “stochastic clonal model.” The pathways that lead to cancer have been delineated genetically and epigenetically. In addition, posttranslational players such as miRNA are now known to have a significant role in cancer diagnosis. To meet the high demands of rapidly proliferating cancer cells, alterations of nutrient and metabolic pathways are required. Accordingly, tumor physiology and the cancer microenvironment have been extensively studied due to their significant role in malignancy. This chapter will discuss these topics and provide a detailed investigation of cancer biology including identification of many of the genes, proteins, signals, and other factors involved in tumorigenesis.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Visvader JE (2011) Cells of origin in cancer. Nature 469(7330):314–322

    CAS  PubMed  Google Scholar 

  2. Lobo NA, Shimono Y, Qian D, Clarke MF (2007) The biology of cancer stem cells. Annu Rev Cell Dev Biol 23(1):675–699. doi:10.1146/annurev.cellbio.22.010305.104154

    CAS  PubMed  Google Scholar 

  3. Harrington L (2004) Does the reservoir for self-renewal stem from the ends? Oncogene 23(43):7283–7289

    CAS  PubMed  Google Scholar 

  4. Reya T, Morrison SJ, Clarke MF, Weissman IL (2001) Stem cells, cancer, and cancer stem cells. Nature 414(6859):105–111. doi:10.1038/35102167

    CAS  PubMed  Google Scholar 

  5. Bruce WR, Van Der Gaag H (1963) A quantitative assay for the number of murine lymphoma cells capable of proliferation in vivo. Nat Cell Biol 199:79–80

    CAS  Google Scholar 

  6. Bergsagel DE, Valeriote FA (1968) Growth characteristics of a mouse plasma cell tumor. Cancer Res 28(11):2187–2196

    CAS  PubMed  Google Scholar 

  7. Park CH, Bergsagel DE, McCulloch EA (1971) Mouse myeloma tumor stem cells: a primary cell culture assay. J Natl Cancer Inst 46(2):411–422

    CAS  PubMed  Google Scholar 

  8. Guo W, Lasky JL, Wu H (2006) Cancer stem cells. Pediatr Res 59(S4):59R–64R

    PubMed  Google Scholar 

  9. Holyoake T, Jiang X, Eaves C, Eaves A (1999) Isolation of a highly quiescent subpopulation of primitive leukemic cells in chronic myeloid leukemia. Blood 94(6):2056–2064

    CAS  PubMed  Google Scholar 

  10. Takahashi N, Miura I, Saitoh K, Miura AB (1998) Lineage involvement of stem cells bearing the philadelphia chromosome in chronic myeloid leukemia in the chronic phase as shown by a combination of fluorescence-activated cell sorting and fluorescence in situ hybridization. Blood 92(12):4758–4763

    CAS  PubMed  Google Scholar 

  11. Hill RP (2006) Identifying cancer stem cells in solid tumors: case not proven. Cancer Res 66(4):1891–1896. doi:10.1158/0008-5472.can-05-3450

    CAS  PubMed  Google Scholar 

  12. Jordan CT, Guzman ML, Noble M (2006) Cancer stem cells. N Engl J Med 355(12):1253–1261. doi:10.1056/NEJMra061808

    CAS  PubMed  Google Scholar 

  13. Brabletz T, Jung A, Spaderna S, Hlubek F, Kirchner T (2005) Opinion: migrating cancer stem cells—an integrated concept of malignant tumour progression. Nat Rev Cancer 5(9):744–749. doi:10.1038/nrc1694

    CAS  PubMed  Google Scholar 

  14. Bonnet D, Dick JE (1997) Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 3(7):730–737

    CAS  PubMed  Google Scholar 

  15. Castor A, Nilsson L, Astrand-Grundstrom I, Buitenhuis M, Ramirez C, Anderson K, Strombeck B, Garwicz S, Bekassy AN, Schmiegelow K, Lausen B, Hokland P, Lehmann S, Juliusson G, Johansson B, Jacobsen SE (2005) Distinct patterns of hematopoietic stem cell involvement in acute lymphoblastic leukemia. Nat Med 11(6):630–637. doi:10.1038/nm1253

    CAS  PubMed  Google Scholar 

  16. Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB (2004) Identification of human brain tumour initiating cells. Nature 432(7015):396–401. doi:10.1038/nature03128

    CAS  PubMed  Google Scholar 

  17. Taylor MD, Poppleton H, Fuller C, Su X, Liu Y, Jensen P, Magdaleno S, Dalton J, Calabrese C, Board J, Macdonald T, Rutka J, Guha A, Gajjar A, Curran T, Gilbertson RJ (2005) Radial glia cells are candidate stem cells of ependymoma. Cancer Cell 8(4):323–335. doi:10.1016/j.ccr.2005.09.001

    CAS  PubMed  Google Scholar 

  18. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A 100(7):3983–3988. doi:10.1073/pnas.0530291100

    CAS  PubMed Central  PubMed  Google Scholar 

  19. Fang D, Nguyen TK, Leishear K, Finko R, Kulp AN, Hotz S, Van Belle PA, Xu X, Elder DE, Herlyn M (2005) A tumorigenic subpopulation with stem cell properties in melanomas. Cancer Res 65(20):9328–9337. doi:10.1158/0008-5472.CAN-05-1343

    CAS  PubMed  Google Scholar 

  20. Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB (2004) Identification of human brain tumour initiating cells. Nature 432(7015):396–401, http://www.nature.com/nature/journal/v432/n7015/suppinfo/nature03128_S1.html

    CAS  PubMed  Google Scholar 

  21. Sanai N, Alvarez-Buylla A, Berger MS (2005) Neural stem cells and the origin of gliomas. N Engl J Med 353(8):811–822. doi:10.1056/NEJMra043666

    CAS  PubMed  Google Scholar 

  22. Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ (2005) Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res 65(23):10946–10951. doi:10.1158/0008-5472.can-05-2018

    CAS  PubMed  Google Scholar 

  23. Gibbs CP, Kukekov VG, Reith JD, Tchigrinova O, Suslov ON, Scott EW, Ghivizzani SC, Ignatova TN, Steindler DA (2005) Stem-like cells in bone sarcomas: implications for tumorigenesis. Neoplasia 7(11):967–976

    CAS  PubMed Central  PubMed  Google Scholar 

  24. Wicha MS, Liu S, Dontu G (2006) Cancer stem cells: an old idea—a paradigm shift. Cancer Res 66(4):1883–1890. doi:10.1158/0008-5472.can-05-3153

    CAS  PubMed  Google Scholar 

  25. Wang JCY, Dick JE (2005) Cancer stem cells: lessons from leukemia. Trends Cell Biol 15(9):494–501. doi:10.1016/j.tcb.2005.07.004

    CAS  PubMed  Google Scholar 

  26. Huntly BJP, Gilliland DG (2005) Leukaemia stem cells and the evolution of cancer-stem-cell research. Nat Rev Cancer 5(4):311–321

    CAS  PubMed  Google Scholar 

  27. Odoux C, Fohrer H, Hoppo T, Guzik L, Stolz DB, Lewis DW, Gollin SM, Gamblin TC, Geller DA, Lagasse E (2008) A stochastic model for cancer stem cell origin in metastatic colon cancer. Cancer Res 68(17):6932–6941. doi:10.1158/0008-5472.can-07-5779

    CAS  PubMed Central  PubMed  Google Scholar 

  28. Krivtsov AV, Twomey D, Feng Z, Stubbs MC, Wang Y, Faber J, Levine JE, Wang J, Hahn WC, Gilliland DG, Golub TR, Armstrong SA (2006) Transformation from committed progenitor to leukaemia stem cell initiated by MLL–AF9. Nature 442(7104):818–822, http://www.nature.com/nature/journal/v442/n7104/suppinfo/nature04980_S1.html

    CAS  PubMed  Google Scholar 

  29. Cho RW, Wang X, Diehn M, Shedden K, Chen GY, Sherlock G, Gurney A, Lewicki J, Clarke MF (2008) Isolation and molecular characterization of cancer stem cells in MMTV-Wnt-1 murine breast tumors. Stem Cells 26(2):364–371. doi:10.1634/stemcells.2007-0440

    CAS  PubMed  Google Scholar 

  30. Vaillant F, Asselin-Labat M-L, Shackleton M, Forrest NC, Lindeman GJ, Visvader JE (2008) The mammary progenitor marker CD61/β3 integrin identifies cancer stem cells in mouse models of mammary tumorigenesis. Cancer Res 68(19):7711–7717. doi:10.1158/0008-5472.can-08-1949

    CAS  PubMed  Google Scholar 

  31. Zhang M, Behbod F, Atkinson RL, Landis MD, Kittrell F, Edwards D, Medina D, Tsimelzon A, Hilsenbeck S, Green JE, Michalowska AM, Rosen JM (2008) Identification of tumor-Initiating cells in a p53-null mouse model of breast cancer. Cancer Res 68(12):4674–4682. doi:10.1158/0008-5472.can-07-6353

    CAS  PubMed Central  PubMed  Google Scholar 

  32. Malanchi I, Peinado H, Kassen D, Hussenet T, Metzger D, Chambon P, Huber M, Hohl D, Cano A, Birchmeier W, Huelsken J (2008) Cutaneous cancer stem cell maintenance is dependent on [bgr]-catenin signalling. Nature 452(7187):650–653, http://www.nature.com/nature/journal/v452/n7187/suppinfo/nature06835_S1.html

    CAS  PubMed  Google Scholar 

  33. Feinberg AP, Ohlsson R, Henikoff S (2006) The epigenetic progenitor origin of human cancer. Nat Rev Genet 7(1):21–33

    CAS  PubMed  Google Scholar 

  34. Iacobuzio-Donahue CA (2009) Epigenetic changes in cancer. Annu Rev Pathol 4(1):229–249. doi:10.1146/annurev.pathol.3.121806.151442

    CAS  PubMed  Google Scholar 

  35. Nordling CO (1953) A new theory on cancer-inducing mechanism. Br J Cancer 7(1):68–72

    CAS  PubMed Central  PubMed  Google Scholar 

  36. Knudson AG Jr (1971) Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A 68(4):820–823

    PubMed Central  PubMed  Google Scholar 

  37. Chial H (2008) Tumor suppressor (TS) genes and the two-hit hypothesis. Nat Educ 1(1)

    Google Scholar 

  38. Lodish H, Berk A, Zipursky SL et al (2000) Section 24.2, Proto-oncogenes and tumor-suppressor genes. In: Molecular cell biology, 4th edn. W. H. Freeman, New York

    Google Scholar 

  39. Chellappan SP, Hiebert S, Mudryj M, Horowitz JM, Nevins JR (1991) The E2F transcription factor is a cellular target for the RB protein. Cell 65(6):1053–1061

    CAS  PubMed  Google Scholar 

  40. Dyson N, Howley PM, Munger K, Harlow E (1989) The human papilloma virus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product. Science 243(4893):934–937

    CAS  PubMed  Google Scholar 

  41. Jiang W, Kahn SM, Tomita N, Zhang YJ, Lu SH, Weinstein IB (1992) Amplification and expression of the human cyclin D gene in esophageal cancer. Cancer Res 52(10):2980–2983

    CAS  PubMed  Google Scholar 

  42. Weinberg RA (1995) The retinoblastoma protein and cell cycle control. Cell 81(3):323–330

    CAS  PubMed  Google Scholar 

  43. Vermeulen K, Van Bockstaele DR, Berneman ZN (2003) The cell cycle: a review of regulation, deregulation and therapeutic targets in cancer. Cell Prolif 36(3):131–149

    CAS  PubMed  Google Scholar 

  44. Efeyan A, Serrano M (2007) p53: guardian of the genome and policeman of the oncogenes. Cell Cycle 6(9):1006–1010

    CAS  PubMed  Google Scholar 

  45. Mossalam M, Matissek KJ, Okal A, Constance JE, Lim CS (2012) Direct induction of apoptosis using an optimal mitochondrially targeted p53. Mol Pharm 9(5):1449–1458. doi:10.1021/mp3000259

    CAS  PubMed Central  PubMed  Google Scholar 

  46. Meek DW (2009) Tumour suppression by p53: a role for the DNA damage response? Nat Rev Cancer 9(10):714–723

    CAS  PubMed  Google Scholar 

  47. Espinosa JM (2008) Mechanisms of regulatory diversity within the p53 transcriptional network. Oncogene 27(29):4013–4023. doi:10.1038/onc.2008.37

    CAS  PubMed Central  PubMed  Google Scholar 

  48. Murray-Zmijewski F, Slee EA, Lu X (2008) A complex barcode underlies the heterogeneous response of p53 to stress. Nat Rev Mol Cell Biol 9(9):702–712

    CAS  PubMed  Google Scholar 

  49. Sherr CJ, Weber JD (2000) The ARF/p53 pathway. Curr Opin Genet Dev 10(1):94–99. doi:10.1016/s0959-437x(99)00038-6

    CAS  PubMed  Google Scholar 

  50. Stewart ZA, Leach SD, Pietenpol JA (1999) p21(Waf1/Cip1) inhibition of cyclin E/Cdk2 activity prevents endoreduplication after mitotic spindle disruption. Mol Cell Biol 19(1):205–215

    CAS  PubMed Central  PubMed  Google Scholar 

  51. Blanco-Aparicio C, Renner O, Leal JF, Carnero A (2007) PTEN, more than the AKT pathway. Carcinogenesis 28(7):1379–1386. doi:10.1093/carcin/bgm052

    CAS  PubMed  Google Scholar 

  52. Suzuki A, de la Pompa JL, Stambolic V, Elia AJ, Sasaki T, del Barco Barrantes I, Ho A, Wakeham A, Ltie A, Khoo W, Fukumoto M, Mak TW (1998) High cancer susceptibility and embryonic lethality associated with mutation of the PTEN tumor suppressor gene in mice. Curr Biol 8(21):1169–1178. doi:10.1016/s0960-9822(07)00488-5

    CAS  PubMed  Google Scholar 

  53. Cristofano AD, Pesce B, Cordon-Cardo C, Pandolfi PP (1998) Pten is essential for embryonic development and tumour suppression. Nat Genet 19(4):348–355

    PubMed  Google Scholar 

  54. Kufe DW, Pollock RE, Weichselbaum RR et al (eds) (2003) Holland-frei cancer medicine, 6th edn. BC Decker, Hamilton, ON

    Google Scholar 

  55. Bos JL (1989) Ras oncogenes in human cancer: a review. Cancer Res 49(17):4682–4689

    CAS  PubMed  Google Scholar 

  56. Minamoto T, Mai M, Ronai Z (2000) K-ras mutation: early detection in molecular diagnosis and risk assessment of colorectal, pancreas, and lung cancers—a review. Cancer Detect Prev 24(1):1–12

    CAS  PubMed  Google Scholar 

  57. Beaupre DM, Kurzrock R (1999) RAS and leukemia: from basic mechanisms to gene-directed therapy. J Clin Oncol 17(3):1071–1079

    CAS  PubMed  Google Scholar 

  58. Adjei AA (2001) Blocking oncogenic ras signaling for cancer therapy. J Natl Cancer Inst 93(14):1062–1074

    CAS  PubMed  Google Scholar 

  59. Kolch W (2000) Meaningful relationships: the regulation of the Ras/Raf/MEK/ERK pathway by protein interactions. Biochem J 351(Pt 2):289–305

    CAS  PubMed  Google Scholar 

  60. Oster SK, Ho CS, Soucie EL, Penn LZ (2002) The myc oncogene: marvelouslY complex. Adv Cancer Res 84:81–154

    CAS  PubMed  Google Scholar 

  61. Brison O (1993) Gene amplification and tumor progression. Biochim Biophys Acta 1155(1):25–41

    CAS  PubMed  Google Scholar 

  62. Brodeur G, Seeger R, Schwab M, Varmus H, Bishop J (1984) Amplification of N-myc in untreated human neuroblastomas correlates with advanced disease stage. Science 224(4653):1121–1124. doi:10.1126/science.6719137

    CAS  PubMed  Google Scholar 

  63. Spandidos DA, Anderson ML (1989) Oncogenes and onco-suppressor genes: their involvement in cancer. J Pathol 157(1):1–10. doi:10.1002/path.1711570102

    CAS  PubMed  Google Scholar 

  64. Bouchard C, Thieke K, Maier A, Saffrich R, Hanley-Hyde J, Ansorge W, Reed S, Sicinski P, Bartek J, Eilers M (1999) Direct induction of cyclin D2 by Myc contributes to cell cycle progression and sequestration of p27. EMBO J 18(19):5321–5333. doi:10.1093/emboj/18.19.5321

    CAS  PubMed  Google Scholar 

  65. van Riggelen J, Yetil A, Felsher DW (2010) MYC as a regulator of ribosome biogenesis and protein synthesis. Nat Rev Cancer 10(4):301–309

    PubMed  Google Scholar 

  66. Gartel AL, Ye X, Goufman E, Shianov P, Hay N, Najmabadi F, Tyner AL (2001) Myc represses the p21(WAF1/CIP1) promoter and interacts with Sp1/Sp3. Proc Natl Acad Sci U S A 98(8):4510–4515. doi:10.1073/pnas.081074898

    CAS  PubMed Central  PubMed  Google Scholar 

  67. Ross JS, Fletcher JA (1999) HER-2/neu (c-erb-B2) gene and protein in breast cancer. Am JClin Pathol 112(1 Suppl 1):S53–S67

    CAS  Google Scholar 

  68. Falini B, Mason DY (2002) Proteins encoded by genes involved in chromosomal alterations in lymphoma and leukemia: clinical value of their detection by immunocytochemistry. Blood 99(2):409–426

    CAS  PubMed  Google Scholar 

  69. Heerema NA (1998) Chromosomes in lymphomas and solid tumors. Cancer Invest 16(3):183–187

    CAS  PubMed  Google Scholar 

  70. Blume-Jensen P, Hunter T (2001) Oncogenic kinase signalling. Nature 411(6835):355–365. doi:10.1038/35077225

    CAS  PubMed  Google Scholar 

  71. Deininger MWN, Goldman JM, Melo JV (2000) The molecular biology of chronic myeloid leukemia. Blood 96(10):3343–3356

    CAS  PubMed  Google Scholar 

  72. Edwards RP, Lee JM, Blackburn P (2012) Ovarian cancer. http://www.emedicinehealth.com/ovarian_cancer/article_em.htm. Accessed 2 Aug 2012

  73. Vogelstein B, Kinzler KW (2004) Cancer genes and the pathways they control. Nat Med 10(8):789–799

    CAS  PubMed  Google Scholar 

  74. Davis CP (2012) Brain cancer. http://www.emedicinehealth.com/brain_cancer/article_em.htm. Accessed 2 Aug 2012

  75. Conrad Stoppler M (2012) Breast cancer. http://www.emedicinehealth.com/breast_cancer/article_em.htm. Accessed 2 Aug 2012

  76. Fingerote RJ (2012) Colon cancer. http://www.emedicinehealth.com/colon_cancer/article_em.htm. Accessed 2 Aug 2012

  77. Conrad Stoppler M (2012) Lung cancer. http://www.emedicinehealth.com/lung_cancer/article_em.htm. Accessed 2 Aug 2012

  78. Stuart KE (2012) Liver cancer. http://www.emedicinehealth.com/liver_cancer/article_em.htm. Accessed 2 Aug 2012

  79. Benowitz S (2007) Liver cancer biomarkers struggling to succeed. J Natl Cancer Inst 99(8):590–591. doi:99/8/590 [pii] 10.1093/jnci/djk174

    PubMed  Google Scholar 

  80. Mao Y, Yang H, Xu H, Lu X, Sang X, Du S, Zhao H, Chen W, Xu Y, Chi T, Yang Z, Cai J, Li H, Chen J, Zhong S, Mohanti SR, Lopez-Soler R, Millis JM, Huang J, Zhang H (2010) Golgi protein 73 (GOLPH2) is a valuable serum marker for hepatocellular carcinoma. Gut 59(12):1687–1693. doi:gut.2010.214916 [pii] 10.1136/gut.2010.214916

    CAS  PubMed  Google Scholar 

  81. Kuo T, Fisher G (2012) Pancreatic cancer. http://www.emedicinehealth.com/pancreatic_cancer/article_em.htm. Accessed 2 Aug 2012

  82. Kelber JA, Reno T, Kaushal S, Metildi C, Wright T, Stoletov K, Weems JM, Park FD, Mose E, Wang Y, Hoffman RM, Lowy AM, Bouvet M, Klemke RL (2012) KRas induces a Src/PEAK1/ErbB2 kinase amplification loop that drives metastatic growth and therapy resistance in pancreatic cancer. Cancer Res 72(10):2554–2564. doi:72/10/2554 [pii] 10.1158/0008-5472.CAN-11-3552

    CAS  PubMed Central  PubMed  Google Scholar 

  83. Harsha HC, Kandasamy K, Ranganathan P, Rani S, Ramabadran S, Gollapudi S, Balakrishnan L, Dwivedi SB, Telikicherla D, Selvan LD, Goel R, Mathivanan S, Marimuthu A, Kashyap M, Vizza RF, Mayer RJ, Decaprio JA, Srivastava S, Hanash SM, Hruban RH, Pandey A (2009) A compendium of potential biomarkers of pancreatic cancer. PLoS Med 6(4):e1000046. doi:10.1371/journal.pmed.1000046

    CAS  PubMed Central  PubMed  Google Scholar 

  84. Zorn KC, Gautam G (2012) Prostate cancer. http://www.emedicinehealth.com/prostate_cancer/article_em.htm. Accessed 2 Aug 2012

  85. Makarov DV, Loeb S, Getzenberg RH, Partin AW (2009) Biomarkers for prostate cancer. Annu Rev Med 60:139–151. doi:10.1146/annurev.med.60.042307.110714

    CAS  PubMed  Google Scholar 

  86. Lapointe J, Li C, Higgins JP, van de Rijn M, Bair E, Montgomery K, Ferrari M, Egevad L, Rayford W, Bergerheim U, Ekman P, DeMarzo AM, Tibshirani R, Botstein D, Brown PO, Brooks JD, Pollack JR (2004) Gene expression profiling identifies clinically relevant subtypes of prostate cancer. Proc Natl Acad Sci U S A 101(3):811–816. doi:10.1073/pnas.0304146101 0304146101 [pii]

    CAS  PubMed Central  PubMed  Google Scholar 

  87. Taylor BS, Schultz N, Hieronymus H, Gopalan A, Xiao Y, Carver BS, Arora VK, Kaushik P, Cerami E, Reva B, Antipin Y, Mitsiades N, Landers T, Dolgalev I, Major JE, Wilson M, Socci ND, Lash AE, Heguy A, Eastham JA, Scher HI, Reuter VE, Scardino PT, Sander C, Sawyers CL, Gerald WL (2010) Integrative genomic profiling of human prostate cancer. Cancer Cell 18(1):11–22. doi:S1535-6108(10)00238-2 [pii] 10.1016/j.ccr.2010.05.026

    CAS  PubMed Central  PubMed  Google Scholar 

  88. Sachdeva K, Curti B (2012) Renal cell cancer. http://www.emedicinehealth.com/renal_cell_cancer/article_em.htm. Accessed 2 Aug 2012

  89. Linehan WM, Srinivasan R, Schmidt LS (2010) The genetic basis of kidney cancer: a metabolic disease. Nat Rev Urol 7(5):277–285. doi:nrurol.2010.47 [pii] 10.1038/nrurol.2010.47

    CAS  PubMed Central  PubMed  Google Scholar 

  90. GrØNbÆK K, Hother C, Jones PA (2007) Epigenetic changes in cancer. Acta Pathol Microbiol Immunol Scand 115(10):1039–1059. doi:10.1111/j.1600-0463.2007.apm_636.xml.x

    Google Scholar 

  91. Ehrlich M, Gama-Sosa MA, Huang LH, Midgett RM, Kuo KC, McCune RA, Gehrke C (1982) Amount and distribution of 5-methylcytosine in human DNA from different types of tissues of cells. Nucleic Acids Res 10(8):2709–2721

    CAS  PubMed Central  PubMed  Google Scholar 

  92. Rideout WM III, Coetzee GA, Olumi AF, Jones PA (1990) 5-Methylcytosine as an endogenous mutagen in the human LDL receptor and p53 genes. Science 249(4974):1288–1290

    CAS  PubMed  Google Scholar 

  93. Nakayama M, Wada M, Harada T, Nagayama J, Kusaba H, Ohshima K, Kozuru M, Komatsu H, Ueda R, Kuwano M (1998) Hypomethylation status of CpG sites at the promoter region and overexpression of the human MDR1 gene in acute myeloid leukemias. Blood 92(11):4296–4307

    CAS  PubMed  Google Scholar 

  94. Herman JG, Baylin SB (2003) Gene silencing in cancer in association with promoter hypermethylation. N Engl J Med 349(21):2042–2054. doi:10.1056/NEJMra023075

    CAS  PubMed  Google Scholar 

  95. Egger G, Liang G, Aparicio A, Jones PA (2004) Epigenetics in human disease and prospects for epigenetic therapy. Nature 429(6990):457–463. doi:10.1038/nature02625

    CAS  PubMed  Google Scholar 

  96. Esteller M (2005) Aberrant DNA methylation as a cancer-inducing mechanism. Annu Rev Pharmacol Toxicol 45:629–656. doi:10.1146/annurev.pharmtox.45.120403.095832

    CAS  PubMed  Google Scholar 

  97. Esteller M, Herman JG (2002) Cancer as an epigenetic disease: DNA methylation and chromatin alterations in human tumours. J Pathol 196(1):1–7. doi:10.1002/path.1024

    CAS  PubMed  Google Scholar 

  98. Kurdistani SK (2011) Histone modifications in cancer biology and prognosis. Prog Drug Res 67:91–106

    CAS  PubMed  Google Scholar 

  99. Lachner M, O’Carroll D, Rea S, Mechtler K, Jenuwein T (2001) Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature 410(6824):116–120. doi:10.1038/35065132

    CAS  PubMed  Google Scholar 

  100. Santos-Rosa H, Schneider R, Bannister AJ, Sherriff J, Bernstein BE, Emre NC, Schreiber SL, Mellor J, Kouzarides T (2002) Active genes are tri-methylated at K4 of histone H3. Nature 419(6905):407–411. doi:10.1038/nature01080

    CAS  PubMed  Google Scholar 

  101. Margueron R, Trojer P, Reinberg D (2005) The key to development: interpreting the histone code? Curr Opin Genet Dev 15(2):163–176. doi:10.1016/j.gde.2005.01.005

    CAS  PubMed  Google Scholar 

  102. Baylin SB, Esteller M, Rountree MR, Bachman KE, Schuebel K, Herman JG (2001) Aberrant patterns of DNA methylation, chromatin formation and gene expression in cancer. Hum Mol Genet 10(7):687–692. doi:10.1093/hmg/10.7.687

    CAS  PubMed  Google Scholar 

  103. Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136(2):215–233. doi:10.1016/j.cell.2009.01.002

    CAS  PubMed Central  PubMed  Google Scholar 

  104. Siva AC, Nelson LJ, Fleischer CL, Majlessi M, Becker MM, Vessella RL, Reynolds MA (2009) Molecular assays for the detection of microRNAs in prostate cancer. Mol Cancer 8:17. doi:10.1186/1476-4598-8-17

    PubMed Central  PubMed  Google Scholar 

  105. Jung ME, Berliner JA, Koroniak L, Gugiu BG, Watson AD (2009) improved synthesis of the epoxy isoprostane phospholipid PEIPC and its reactivity with amines. Org Lett 10(19): 4207–4209

    Google Scholar 

  106. Cho WCS (2010) MicroRNAs: potential biomarkers for cancer diagnosis, prognosis and targets for therapy. Int J Biochem Cell Biol 42(8):1273–1281. doi:10.1016/j.biocel.2009.12.014

    CAS  PubMed  Google Scholar 

  107. Bandres E, Bitarte N, Arias F, Agorreta J, Fortes P, Agirre X, Zarate R, Diaz-Gonzalez JA, Ramirez N, Sola JJ, Jimenez P, Rodriguez J, Garcia-Foncillas J (2009) microRNA-451 regulates macrophage migration inhibitory factor production and proliferation of gastrointestinal cancer cells. Clin Cancer Res 15(7):2281–2290. doi:10.1158/1078-0432.ccr-08-1818

    CAS  PubMed  Google Scholar 

  108. Greither T, Grochola LF, Udelnow A, Lautenschläger C, Würl P, Taubert H (2010) Elevated expression of microRNAs 155, 203, 210 and 222 in pancreatic tumors is associated with poorer survival. Int J Cancer 126(1):73–80. doi:10.1002/ijc.24687

    CAS  PubMed  Google Scholar 

  109. Calin GA, Croce CM (2006) MicroRNA signatures in human cancers. Nat Rev Cancer 6(11):857–866

    CAS  PubMed  Google Scholar 

  110. Dyrskjøt L, Ostenfeld MS, Bramsen JB, Silahtaroglu AN, Lamy P, Ramanathan R, Fristrup N, Jensen JL, Andersen CL, Zieger K, Kauppinen S, Ulhøi BP, Kjems J, Borre M, Ørntoft TF (2009) Genomic profiling of MicroRNAs in bladder cancer: miR-129 is associated with poor outcome and promotes cell death in vitro. Cancer Res 69(11):4851–4860. doi:10.1158/0008-5472.can-08-4043

    PubMed  Google Scholar 

  111. Hui ABY, Shi W, Boutros PC, Miller N, Pintilie M, Fyles T, McCready D, Wong D, Gerster K, Jurisica I, Penn LZ, Liu F-F (2009) Robust global micro-RNA profiling with formalin-fixed paraffin-embedded breast cancer tissues. Lab Invest 89(5):597–606, http://www.nature.com/labinvest/journal/v89/n5/suppinfo/labinvest200912s1.html

    CAS  PubMed  Google Scholar 

  112. Li J, Huang H, Sun L, Yang M, Pan C, Chen W, Wu D, Lin Z, Zeng C, Yao Y, Zhang P, Song E (2009) MiR-21 indicates poor prognosis in tongue squamous cell carcinomas as an apoptosis inhibitor. Clin Cancer Res 15(12):3998–4008. doi:10.1158/1078-0432.ccr-08-3053

    CAS  PubMed  Google Scholar 

  113. Chen HC, Chen GH, Chen YH, Liao WL, Liu CY, Chang KP, Chang YS, Chen SJ (2009) MicroRNA deregulation and pathway alterations in nasopharyngeal carcinoma. Br J Cancer 100(6):1002–1011, http://www.nature.com/bjc/journal/v100/n6/suppinfo/6604948s1.html

    CAS  PubMed Central  PubMed  Google Scholar 

  114. Gibcus JH, Tan LP, Harms G, Schakel RN, De Jong D, Blokzijl T, Möller P, Poppema S, Kroesen BJ, Van Den Berg A (2009) Hodgkin lymphoma cell lines are characterized by a specific miRNA expression profile. Neoplasia 11(2):167–176

    CAS  PubMed Central  PubMed  Google Scholar 

  115. Greither T, Grochola LF, Udelnow A, Lautenschläger C, Würl P, Taubert H (2010) Elevated expression of microRNAs 155, 203, 210 and 222 in pancreatic tumors is associated with poorer survival. Int J Cancer 126(1):73–80

    CAS  PubMed  Google Scholar 

  116. Hui AB, Shi W, Boutros PC, Miller N, Pintilie M, Fyles T, McCready D, Wong D, Gerster K, Jurisica I, Penn LZ, Liu FF (2009) Robust global micro-RNA profiling with formalin-fixed paraffin-embedded breast cancer tissues. Lab Invest 89(5):597–606

    CAS  PubMed  Google Scholar 

  117. Jung MN, Koo JE, Oh SJ, Lee BW, Lee WJ, Ha SH, Cho YR, Chang JH (2009) Influence of growth mode on the structural, optical, and electrical properties of in-doped ZnO nanorods. Appl Phys Lett 94(4):041906

    Google Scholar 

  118. Veerla S, Lindgren D, Kvist A, Frigyesi A, Staaf J, Persson H, Liedberg F, Chebil G, Gudjonsson S, Borg Å, Månsson W, Rovira C, Höglund M (2009) MiRNA expression in urothelial carcinomas: important roles of miR-10a, miR-222, miR-125b, miR-7 and miR-452 for tumor stage and metastasis, and frequent homozygous losses of miR-31. Int J Cancer 124(9):2236–2242

    CAS  PubMed  Google Scholar 

  119. Stamatopoulos B, Meuleman N, Haibe-Kains B, Saussoy P, Van Den Neste E, Michaux L, Heimann P, Martiat P, Bron D, Lagneaux L (2009) microRNA-29c and microRNA-223 down-regulation has in vivo significance in chronic lymphocytic leukemia and improves disease risk stratification. Blood 113(21):5237–5245

    CAS  PubMed  Google Scholar 

  120. Xu H, Cheung IY, Guo HF, Cheung NKV (2009) MicroRNA miR-29 modulates expression of immunoinhibitory molecule B7-H3: potential implications for immune based therapy of human solid tumors. Cancer Res 69(15):6275–6281

    CAS  PubMed Central  PubMed  Google Scholar 

  121. Chen HC, Chen GH, Chen YH, Liao WL, Liu CY, Chang KP, Chang YS, Chen SJ (2009) MicroRNA deregulation and pathway alterations in nasopharyngeal carcinoma. Br J Cancer 100(6):1002–1011

    CAS  PubMed Central  PubMed  Google Scholar 

  122. Pigazzi M, Manara E, Baron E, Basso G (2009) MiR-34b targets cyclic AMP-responsive element binding protein in acute myeloid leukemia. Cancer Res 69(6):2471–2478

    CAS  PubMed  Google Scholar 

  123. Zenz T, Mohr J, Eldering E, Kater AP, Bühler A, Kienle D, Winkler D, Dürig J, Van Oers MHJ, Mertens D, Döhner H, Stilgenbauer S (2009) miR-34a as part of the resistance network in chronic lymphocytic leukemia. Blood 113(16):3801–3808

    CAS  PubMed  Google Scholar 

  124. Bandres E, Agirre X, Bitarte N, Ramirez N, Zarate R, Roman-Gomez J, Prosper F, Garcia-Foncillas J (2009) Epigenetic regulation of microRNA expression in colorectal cancer. Int J Cancer 125(11):2737–2743

    CAS  PubMed  Google Scholar 

  125. Dyrskjøt L, Ostenfeld MS, Bramsen JB, Silahtaroglu AN, Lamy P, Ramanathan R, Fristrup N, Jensen JL, Andersen CL, Zieger K, Kauppinen S, Ulhøi BP, Kjems J, Borre M, Ørntoft TF (2009) Genomic profiling of microRNAs in bladder cancer: miR-129 is associated with poor outcome and promotes cell death in vitro. Cancer Res 69(11):4851–4860

    PubMed  Google Scholar 

  126. Grunt TW, Lametschwandtner A, Staindl O (1985) The vascular pattern of basal cell tumors: light microscopy and scanning electron microscopic study on vascular corrosion casts. Microvasc Res 29(3):371–386

    CAS  PubMed  Google Scholar 

  127. Brown JM, Giaccia AJ (1998) The unique physiology of solid tumors: opportunities (and problems) for cancer therapy. Cancer Res 58(7):1408–1416

    CAS  PubMed  Google Scholar 

  128. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674. doi:S0092-8674(11)00127-9 [pii] 10.1016/j.cell.2011.02.013

    CAS  PubMed  Google Scholar 

  129. Deberardinis RJ, Sayed N, Ditsworth D, Thompson CB (2008) Brick by brick: metabolism and tumor cell growth. Curr Opin Genet Dev 18(1):54–61. doi:10.1016/j.gde.2008.02.003

    CAS  PubMed Central  PubMed  Google Scholar 

  130. Ferreira LM, Hebrant A, Dumont JE (2012) Metabolic reprogramming of the tumor. Oncogene 31(36):3999–4011. doi:10.1038/onc.2011.576

    CAS  PubMed  Google Scholar 

  131. Diaz-Ruiz R, Uribe-Carvajal S, Devin A, Rigoulet M (2009) Tumor cell energy metabolism and its common features with yeast metabolism. Biochim Biophys Acta 1796(2):252–265. doi:10.1016/j.bbcan.2009.07.003

    CAS  PubMed  Google Scholar 

  132. Marty N, Dallaporta M, Thorens B (2007) Brain glucose sensing, counterregulation, and energy homeostasis. Physiology (Bethesda) 22:241–251. doi:10.1152/physiol.00010.2007

    CAS  Google Scholar 

  133. Warburg O, Wind F, Negelein E (1927) The metabolism of tumors in the body. J Gen Physiol 8(6):519–530

    CAS  PubMed Central  PubMed  Google Scholar 

  134. Phelps ME (2000) PET: the merging of biology and imaging into molecular imaging. J Nucl Med 41(4):661–681

    CAS  PubMed  Google Scholar 

  135. Ganapathy V, Thangaraju M, Prasad PD (2009) Nutrient transporters in cancer: relevance to Warburg hypothesis and beyond. Pharmacol Ther 121(1):29–40. doi:10.1016/j.pharmthera.2008.09.005

    CAS  PubMed  Google Scholar 

  136. Reske SN, Grillenberger KG, Glatting G, Port M, Hildebrandt M, Gansauge F, Beger HG (1997) Overexpression of glucose transporter 1 and increased FDG uptake in pancreatic carcinoma. J Nucl Med 38(9):1344–1348

    CAS  PubMed  Google Scholar 

  137. Thorens B, Mueckler M (2010) Glucose transporters in the 21st century. Am J Physiol Endocrinol Metab 298(2):E141–E145. doi:10.1152/ajpendo.00712.2009

    CAS  PubMed  Google Scholar 

  138. Uldry M, Thorens B (2004) The SLC2 family of facilitated hexose and polyol transporters. Pflugers Arch 447(5):480–489. doi:10.1007/s00424-003-1085-0

    CAS  PubMed  Google Scholar 

  139. Mueckler M, Caruso C, Baldwin SA, Panico M, Blench I, Morris HR, Allard WJ, Lienhard GE, Lodish HF (1985) Sequence and structure of a human glucose transporter. Science 229(4717):941–945

    CAS  PubMed  Google Scholar 

  140. Schwartzenberg-Bar-Yoseph F, Armoni M, Karnieli E (2004) The tumor suppressor p53 down-regulates glucose transporters GLUT1 and GLUT4 gene expression. Cancer Res 64(7):2627–2633

    CAS  PubMed  Google Scholar 

  141. Tsukioka M, Matsumoto Y, Noriyuki M, Yoshida C, Nobeyama H, Yoshida H, Yasui T, Sumi T, Honda K, Ishiko O (2007) Expression of glucose transporters in epithelial ovarian carcinoma: correlation with clinical characteristics and tumor angiogenesis. Oncol Rep 18(2):361–367

    CAS  PubMed  Google Scholar 

  142. Tohma T, Okazumi S, Makino H, Cho A, Mochizuki R, Shuto K, Kudo H, Matsubara K, Gunji H, Matsubara H, Ochiai T (2005) Overexpression of glucose transporter 1 in esophageal squamous cell carcinomas: a marker for poor prognosis. Dis Esophagus 18(3):185–189. doi:10.1111/j.1442-2050.2005.00489.x

    CAS  PubMed  Google Scholar 

  143. Kang SS, Chun YK, Hur MH, Lee HK, Kim YJ, Hong SR, Lee JH, Lee SG, Park YK (2002) Clinical significance of glucose transporter 1 (GLUT1) expression in human breast carcinoma. Jpn J Cancer Res 93(10):1123–1128

    CAS  PubMed  Google Scholar 

  144. Berlangieri SU, Scott AM (2000) Metabolic staging of lung cancer. N Engl J Med 343(4):290–292. doi:10.1056/NEJM200007273430410

    CAS  PubMed  Google Scholar 

  145. Suzuki T, Iwazaki A, Katagiri H, Oka Y, Redpath JL, Stanbridge EJ, Kitagawa T (1999) Enhanced expression of glucose transporter GLUT3 in tumorigenic HeLa cell hybrids associated with tumor suppressor dysfunction. Eur J Biochem 262(2):534–540

    CAS  PubMed  Google Scholar 

  146. Kim JW, Tchernyshyov I, Semenza GL, Dang CV (2006) HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab 3(3):177–185. doi:10.1016/j.cmet.2006.02.002

    PubMed  Google Scholar 

  147. Shim H, Dolde C, Lewis BC, Wu CS, Dang G, Jungmann RA, Dalla-Favera R, Dang CV (1997) c-Myc transactivation of LDH-A: implications for tumor metabolism and growth. Proc Natl Acad Sci U S A 94(13):6658–6663

    CAS  PubMed Central  PubMed  Google Scholar 

  148. Reinacher M, Eigenbrodt E (1981) Immunohistological demonstration of the same type of pyruvate kinase isoenzyme (M2-Pk) in tumors of chicken and rat. Virchows Arch B Cell Pathol Incl Mol Pathol 37(1):79–88

    CAS  PubMed  Google Scholar 

  149. Mazurek S, Boschek CB, Hugo F, Eigenbrodt E (2005) Pyruvate kinase type M2 and its role in tumor growth and spreading. Semin Cancer Biol 15(4):300–308. doi:10.1016/j.semcancer.2005.04.009

    CAS  PubMed  Google Scholar 

  150. Feron O (2009) Pyruvate into lactate and back: from the Warburg effect to symbiotic energy fuel exchange in cancer cells. Radiother Oncol 92(3):329–333. doi:10.1016/j.radonc.2009.06.025

    CAS  PubMed  Google Scholar 

  151. Mazurek S, Grimm H, Oehmke M, Weisse G, Teigelkamp S, Eigenbrodt E (2000) Tumor M2-PK and glutaminolytic enzymes in the metabolic shift of tumor cells. Anticancer Res 20(6D):5151–5154

    CAS  PubMed  Google Scholar 

  152. Hoshino A, Hirst JA, Fujii H (2007) Regulation of cell proliferation by interleukin-3-induced nuclear translocation of pyruvate kinase. J Biol Chem 282(24):17706–17711. doi:10.1074/jbc.M700094200

    CAS  PubMed  Google Scholar 

  153. Bensinger SJ, Christofk HR (2012) New aspects of the Warburg effect in cancer cell biology. Semin Cell Dev Biol. doi:10.1016/j.semcdb.2012.02.003

    PubMed  Google Scholar 

  154. Halestrap AP, Meredith D (2004) The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond. Pflugers Arch 447(5):619–628. doi:10.1007/s00424-003-1067-2

    CAS  PubMed  Google Scholar 

  155. Ullah MS, Davies AJ, Halestrap AP (2006) The plasma membrane lactate transporter MCT4, but not MCT1, is up-regulated by hypoxia through a HIF-1alpha-dependent mechanism. J Biol Chem 281(14):9030–9037. doi:10.1074/jbc.M511397200

    CAS  PubMed  Google Scholar 

  156. Li H, Myeroff L, Smiraglia D, Romero MF, Pretlow TP, Kasturi L, Lutterbaugh J, Rerko RM, Casey G, Issa JP, Willis J, Willson JK, Plass C, Markowitz SD (2003) SLC5A8, a sodium transporter, is a tumor suppressor gene silenced by methylation in human colon aberrant crypt foci and cancers. Proc Natl Acad Sci U S A 100(14):8412–8417. doi:10.1073/pnas.1430846100

    CAS  PubMed Central  PubMed  Google Scholar 

  157. Swietach P, Vaughan-Jones RD, Harris AL (2007) Regulation of tumor pH and the role of carbonic anhydrase 9. Cancer Metastasis Rev 26(2):299–310. doi:10.1007/s10555-007-9064-0

    CAS  PubMed  Google Scholar 

  158. Waagepetersen HS, Sonnewald U, Larsson OM, Schousboe A (2000) A possible role of alanine for ammonia transfer between astrocytes and glutamatergic neurons. J Neurochem 75(2):471–479

    CAS  PubMed  Google Scholar 

  159. Kennedy KM, Dewhirst MW (2010) Tumor metabolism of lactate: the influence and therapeutic potential for MCT and CD147 regulation. Future Oncol 6(1):127–148. doi:10.2217/fon.09.145

    CAS  PubMed Central  PubMed  Google Scholar 

  160. Walenta S, Mueller-Klieser WF (2004) Lactate: mirror and motor of tumor malignancy. Semin Radiat Oncol 14(3):267–274. doi:10.1016/j.semradonc.2004.04.004

    PubMed  Google Scholar 

  161. Fischer K, Hoffmann P, Voelkl S, Meidenbauer N, Ammer J, Edinger M, Gottfried E, Schwarz S, Rothe G, Hoves S, Renner K, Timischl B, Mackensen A, Kunz-Schughart L, Andreesen R, Krause SW, Kreutz M (2007) Inhibitory effect of tumor cell-derived lactic acid on human T cells. Blood 109(9):3812–3819. doi:10.1182/blood-2006-07-035972

    CAS  PubMed  Google Scholar 

  162. Heitman J, Movva NR, Hall MN (1991) Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast. Science 253(5022):905–909

    CAS  PubMed  Google Scholar 

  163. Hay N, Sonenberg N (2004) Upstream and downstream of mTOR. Genes Dev 18(16):1926–1945. doi:10.1101/gad.1212704

    CAS  PubMed  Google Scholar 

  164. Nojima H, Tokunaga C, Eguchi S, Oshiro N, Hidayat S, Yoshino K, Hara K, Tanaka N, Avruch J, Yonezawa K (2003) The mammalian target of rapamycin (mTOR) partner, raptor, binds the mTOR substrates p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS) motif. J Biol Chem 278(18):15461–15464. doi:10.1074/jbc.C200665200

    CAS  PubMed  Google Scholar 

  165. Sarbassov DD, Ali SM, Sengupta S, Sheen JH, Hsu PP, Bagley AF, Markhard AL, Sabatini DM (2006) Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Mol Cell 22(2):159–168. doi:10.1016/j.molcel.2006.03.029

    CAS  PubMed  Google Scholar 

  166. Saucedo LJ, Gao X, Chiarelli DA, Li L, Pan D, Edgar BA (2003) Rheb promotes cell growth as a component of the insulin/TOR signalling network. Nat Cell Biol 5(6):566–571. doi:10.1038/ncb996

    CAS  PubMed  Google Scholar 

  167. Charest PG, Shen Z, Lakoduk A, Sasaki AT, Briggs SP, Firtel RA (2010) A Ras signaling complex controls the RasC-TORC2 pathway and directed cell migration. Dev Cell 18(5):737–749. doi:10.1016/j.devcel.2010.03.017

    CAS  PubMed Central  PubMed  Google Scholar 

  168. Dowling RJ, Topisirovic I, Alain T, Bidinosti M, Fonseca BD, Petroulakis E, Wang X, Larsson O, Selvaraj A, Liu Y, Kozma SC, Thomas G, Sonenberg N (2010) mTORC1-mediated cell proliferation, but not cell growth, controlled by the 4E-BPs. Science 328(5982):1172–1176. doi:10.1126/science.1187532

    CAS  PubMed Central  PubMed  Google Scholar 

  169. Ma XM, Blenis J (2009) Molecular mechanisms of mTOR-mediated translational control. Nat Rev Mol Cell Biol 10(5):307–318. doi:10.1038/nrm2672

    PubMed  Google Scholar 

  170. Wilson KF, Wu WJ, Cerione RA (2000) Cdc42 stimulates RNA splicing via the S6 kinase and a novel S6 kinase target, the nuclear cap-binding complex. J Biol Chem 275(48):37307–37310. doi:10.1074/jbc.C000482200

    CAS  PubMed  Google Scholar 

  171. Mayer C, Zhao J, Yuan X, Grummt I (2004) mTOR-dependent activation of the transcription factor TIF-IA links rRNA synthesis to nutrient availability. Genes Dev 18(4):423–434. doi:10.1101/gad.285504

    CAS  PubMed  Google Scholar 

  172. Kamada Y, Funakoshi T, Shintani T, Nagano K, Ohsumi M, Ohsumi Y (2000) Tor-mediated induction of autophagy via an Apg1 protein kinase complex. J Cell Biol 150(6):1507–1513

    CAS  PubMed  Google Scholar 

  173. Zoncu R, Efeyan A, Sabatini DM (2011) mTOR: from growth signal integration to cancer, diabetes and ageing. Nat Rev Mol Cell Biol 12(1):21–35. doi:10.1038/nrm3025

    CAS  PubMed Central  PubMed  Google Scholar 

  174. Facchinetti V, Ouyang W, Wei H, Soto N, Lazorchak A, Gould C, Lowry C, Newton AC, Mao Y, Miao RQ, Sessa WC, Qin J, Zhang P, Su B, Jacinto E (2008) The mammalian target of rapamycin complex 2 controls folding and stability of Akt and protein kinase C. EMBO J 27(14):1932–1943. doi:10.1038/emboj.2008.120

    CAS  PubMed  Google Scholar 

  175. Sarbassov DD, Guertin DA, Ali SM, Sabatini DM (2005) Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 307(5712):1098–1101. doi:10.1126/science.1106148

    CAS  PubMed  Google Scholar 

  176. Sabine JR, Abraham S, Chaikoff IL (1967) Control of lipid metabolism in hepatomas: insensitivity of rate of fatty acid and cholesterol synthesis by mouse hepatoma BW7756 to fasting and to feedback control. Cancer Res 27(4):793–799

    CAS  PubMed  Google Scholar 

  177. Ookhtens M, Kannan R, Lyon I, Baker N (1984) Liver and adipose tissue contributions to newly formed fatty acids in an ascites tumor. Am J Physiol 247(1 Pt 2):R146–R153

    CAS  PubMed  Google Scholar 

  178. Kuhajda FP (2000) Fatty-acid synthase and human cancer: new perspectives on its role in tumor biology. Nutrition 16(3):202–208

    CAS  PubMed  Google Scholar 

  179. Young CD, Anderson SM (2008) Sugar and fat—that’s where it’s at: metabolic changes in tumors. Breast Cancer Res 10(1):202. doi:10.1186/bcr1852

    PubMed Central  PubMed  Google Scholar 

  180. Pizer ES, Wood FD, Pasternack GR, Kuhajda FP (1996) Fatty acid synthase (FAS): a target for cytotoxic antimetabolites in HL60 promyelocytic leukemia cells. Cancer Res 56(4):745–751

    CAS  PubMed  Google Scholar 

  181. Kinlaw WB, Quinn JL, Wells WA, Roser-Jones C, Moncur JT (2006) Spot 14: a marker of aggressive breast cancer and a potential therapeutic target. Endocrinology 147(9):4048–4055. doi:10.1210/en.2006-0463

    CAS  PubMed  Google Scholar 

  182. Nomura DK, Long JZ, Niessen S, Hoover HS, Ng SW, Cravatt BF (2010) Monoacylglycerol lipase regulates a fatty acid network that promotes cancer pathogenesis. Cell 140(1):49–61. doi:10.1016/j.cell.2009.11.027

    CAS  PubMed Central  PubMed  Google Scholar 

  183. Kryukov GV, Castellano S, Novoselov SV, Lobanov AV, Zehtab O, Guigo R, Gladyshev VN (2003) Characterization of mammalian selenoproteomes. Science 300(5624):1439–1443. doi:10.1126/science.1083516

    CAS  PubMed  Google Scholar 

  184. Cheng WH, Ho YS, Ross DA, Valentine BA, Combs GF, Lei XG (1997) Cellular glutathione peroxidase knockout mice express normal levels of selenium-dependent plasma and phospholipid hydroperoxide glutathione peroxidases in various tissues. J Nutr 127(8):1445–1450

    CAS  PubMed  Google Scholar 

  185. de Haan JB, Bladier C, Lotfi-Miri M, Taylor J, Hutchinson P, Crack PJ, Hertzog P, Kola I (2004) Fibroblasts derived from Gpx1 knockout mice display senescent-like features and are susceptible to H2O2-mediated cell death. Free Radic Biol Med 36(1):53–64. doi:10.1016/j.freeradbiomed.2003.10.020

    PubMed  Google Scholar 

  186. Lee DH, Esworthy RS, Chu C, Pfeifer GP, Chu FF (2006) Mutation accumulation in the intestine and colon of mice deficient in two intracellular glutathione peroxidases. Cancer Res 66(20):9845–9851. doi:10.1158/0008-5472.CAN-06-0732

    CAS  PubMed  Google Scholar 

  187. Shen CL, Song W, Pence BC (2001) Interactions of selenium compounds with other antioxidants in DNA damage and apoptosis in human normal keratinocytes. Cancer Epidemiol Biomarkers Prev 10(4):385–390

    CAS  PubMed  Google Scholar 

  188. Zhao R, Domann FE, Zhong W (2006) Apoptosis induced by selenomethionine and methioninase is superoxide mediated and p53 dependent in human prostate cancer cells. Mol Cancer Ther 5(12):3275–3284. doi:10.1158/1535-7163.MCT-06-0400

    CAS  PubMed Central  PubMed  Google Scholar 

  189. Hu H, Jiang C, Schuster T, Li GX, Daniel PT, Lu J (2006) Inorganic selenium sensitizes prostate cancer cells to TRAIL-induced apoptosis through superoxide/p53/Bax-mediated activation of mitochondrial pathway. Mol Cancer Ther 5(7):1873–1882. doi:10.1158/1535-7163.MCT-06-0063

    CAS  PubMed  Google Scholar 

  190. Madsen E, Gitlin JD (2007) Copper deficiency. Curr Opin Gastroenterol 23(2):187–192. doi:10.1097/MOG.0b013e32801421bb

    CAS  PubMed  Google Scholar 

  191. Inutsuka S, Araki S (1978) Plasma copper and zinc levels in patients with malignant tumors of digestive organs: clinical evaluation of the C1/Zn ratio. Cancer 42(2):626–631

    CAS  PubMed  Google Scholar 

  192. Linder MC (2001) Copper and genomic stability in mammals. Mutat Res 475(1–2):141–152

    CAS  PubMed  Google Scholar 

  193. Cheng WH (2009) Impact of inorganic nutrients on maintenance of genomic stability. Environ Mol Mutagen 50(5):349–360. doi:10.1002/em.20489

    CAS  PubMed  Google Scholar 

  194. Pavletich NP, Chambers KA, Pabo CO (1993) The DNA-binding domain of p53 contains the four conserved regions and the major mutation hot spots. Genes Dev 7(12B):2556–2564

    CAS  PubMed  Google Scholar 

  195. Bleijlevens B, Shivarattan T, Sedgwick B, Rigby SE, Matthews SJ (2007) Replacement of non-heme Fe(II) with Cu(II) in the alpha-ketoglutarate dependent DNA repair enzyme AlkB: spectroscopic characterization of the active site. J Inorg Biochem 101(7):1043–1048. doi:10.1016/j.jinorgbio.2007.03.018

    CAS  PubMed  Google Scholar 

  196. Ridley AJ, Schwartz MA, Burridge K, Firtel RA, Ginsberg MH, Borisy G, Parsons JT, Horwitz AR (2003) Cell migration: integrating signals from front to back. Science 302(5651):1704–1709. doi:10.1126/science.1092053

    CAS  PubMed  Google Scholar 

  197. Giannone G, Ronde P, Gaire M, Beaudouin J, Haiech J, Ellenberg J, Takeda K (2004) Calcium rises locally trigger focal adhesion disassembly and enhance residency of focal adhesion kinase at focal adhesions. J Biol Chem 279(27):28715–28723. doi:10.1074/jbc.M404054200

    CAS  PubMed  Google Scholar 

  198. Schneider M, Hansen JL, Sheikh SP (2008) S100A4: a common mediator of epithelial-mesenchymal transition, fibrosis and regeneration in diseases? J Mol Med (Berl) 86(5):507–522. doi:10.1007/s00109-007-0301-3

    CAS  Google Scholar 

  199. Mbeunkui F, Johann DJ Jr (2009) Cancer and the tumor microenvironment: a review of an essential relationship. Cancer Chemother Pharmacol 63(4):571–582. doi:10.1007/s00280-008-0881-9

    PubMed Central  PubMed  Google Scholar 

  200. Whiteside TL (2008) The tumor microenvironment and its role in promoting tumor growth. Oncogene 27(45):5904–5912. doi:onc2008271 [pii] 10.1038/onc.2008.271

    CAS  PubMed Central  PubMed  Google Scholar 

  201. Tlsty TD, Coussens LM (2006) Tumor stroma and regulation of cancer development. Annu Rev Pathol 1:119–150. doi:10.1146/annurev.pathol.1.110304.100224

    CAS  PubMed  Google Scholar 

  202. Sund M, Kalluri R (2009) Tumor stroma derived biomarkers in cancer. Cancer Metastasis Rev 28(1–2):177–183. doi:10.1007/s10555-008-9175-2

    PubMed  Google Scholar 

  203. De Wever O, Demetter P, Mareel M, Bracke M (2008) Stromal myofibroblasts are drivers of invasive cancer growth. Int J Cancer 123(10):2229–2238. doi:10.1002/ijc.23925

    PubMed  Google Scholar 

  204. Xing F, Saidou J, Watabe K (2010) Cancer associated fibroblasts (CAFs) in tumor microenvironment. Front Biosci 15:166–179. doi:3613 [pii]

    CAS  Google Scholar 

  205. Kalluri R, Zeisberg M (2006) Fibroblasts in cancer. Nat Rev Cancer 6(5):392–401. doi:nrc1877 [pii]10.1038/nrc1877

    CAS  PubMed  Google Scholar 

  206. Mantovani A, Sozzani S, Locati M, Allavena P, Sica A (2002) Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol 23(11):549–555

    CAS  PubMed  Google Scholar 

  207. Ochoa AC, Zea AH, Hernandez C, Rodriguez PC (2007) Arginase, prostaglandins, and myeloid-derived suppressor cells in renal cell carcinoma. Clin Cancer Res 13(2 Pt 2):721s–726s. doi:10.1158/1078-0432.CCR-06-2197

    CAS  PubMed  Google Scholar 

  208. Smyth MJ, Cretney E, Kershaw MH, Hayakawa Y (2004) Cytokines in cancer immunity and immunotherapy. Immunol Rev 202:275–293. doi:IMR199 [pii] 10.1111/j.0105-2896.2004.00199.x

    CAS  PubMed  Google Scholar 

  209. Balkwill FR (2012) The chemokine system and cancer. J Pathol 226(2):148–157. doi:10.1002/path.3029

    CAS  PubMed  Google Scholar 

  210. Balkwill F (2004) Cancer and the chemokine network. Nat Rev Cancer 4(7):540–550. doi:10.1038/nrc1388 nrc1388 [pii]

    CAS  PubMed  Google Scholar 

  211. Bornstein P, Sage EH (2002) Matricellular proteins: extracellular modulators of cell function. Curr Opin Cell Biol 14(5):608–616

    CAS  PubMed  Google Scholar 

  212. Raines EW, Lane TF, Iruela-Arispe ML, Ross R, Sage EH (1992) The extracellular glycoprotein SPARC interacts with platelet-derived growth factor (PDGF)-AB and -BB and inhibits the binding of PDGF to its receptors. Proc Natl Acad Sci U S A 89(4):1281–1285

    CAS  PubMed Central  PubMed  Google Scholar 

  213. Hasselaar P, Sage EH (1992) SPARC antagonizes the effect of basic fibroblast growth factor on the migration of bovine aortic endothelial cells. J Cell Biochem 49(3):272–283. doi:10.1002/jcb.240490310

    CAS  PubMed  Google Scholar 

  214. Porter PL, Sage EH, Lane TF, Funk SE, Gown AM (1995) Distribution of SPARC in normal and neoplastic human tissue. J Histochem Cytochem 43(8):791–800

    CAS  PubMed  Google Scholar 

  215. Alonso SR, Tracey L, Ortiz P, Perez-Gomez B, Palacios J, Pollan M, Linares J, Serrano S, Saez-Castillo AI, Sanchez L, Pajares R, Sanchez-Aguilera A, Artiga MJ, Piris MA, Rodriguez-Peralto JL (2007) A high-throughput study in melanoma identifies epithelial-mesenchymal transition as a major determinant of metastasis. Cancer Res 67(7):3450–3460. doi:10.1158/0008-5472.CAN-06-3481

    CAS  PubMed  Google Scholar 

  216. Smit DJ, Gardiner BB, Sturm RA (2007) Osteonectin downregulates E-cadherin, induces osteopontin and focal adhesion kinase activity stimulating an invasive melanoma phenotype. Int J Cancer 121(12):2653–2660. doi:10.1002/ijc.23039

    CAS  PubMed  Google Scholar 

  217. Bergers G, Song S (2005) The role of pericytes in blood-vessel formation and maintenance. Neuro Oncol 7(4):452–464. doi:10.1215/S1152851705000232

    CAS  PubMed Central  PubMed  Google Scholar 

  218. Gaengel K, Genove G, Armulik A, Betsholtz C (2009) Endothelial-mural cell signaling in vascular development and angiogenesis. Arterioscler Thromb Vasc Biol 29(5):630–638. doi:10.1161/ATVBAHA.107.161521

    CAS  PubMed  Google Scholar 

  219. Folkman J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285(21):1182–1186. doi:10.1056/NEJM197111182852108

    CAS  PubMed  Google Scholar 

  220. Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100(1):57–70. doi:S0092-8674(00)81683-9 [pii]

    CAS  PubMed  Google Scholar 

  221. Poon RT, Fan ST, Wong J (2001) Clinical implications of circulating angiogenic factors in cancer patients. J Clin Oncol 19(4):1207–1225

    CAS  PubMed  Google Scholar 

  222. Bridges EM, Harris AL (2011) The angiogenic process as a therapeutic target in cancer. Biochem Pharmacol 81(10):1183–1191. doi:S0006-2952(11)00120-1 [pii] 10.1016/j.bcp.2011.02.016

    CAS  PubMed  Google Scholar 

  223. Tortora G, Melisi D, Ciardiello F (2004) Angiogenesis: a target for cancer therapy. Curr Pharm Des 10(1):11–26

    CAS  PubMed  Google Scholar 

  224. Huang Z, Bao SD (2004) Roles of main pro- and anti-angiogenic factors in tumor angiogenesis. World J Gastroenterol 10(4):463–470

    CAS  PubMed  Google Scholar 

  225. Weinberg RA (2007) The biology of cancer. Garland Science, Taylor & Francis Group, New York

    Google Scholar 

  226. Valastyan S, Weinberg RA (2011) Tumor metastasis: molecular insights and evolving paradigms. Cell 147(2):275–292. doi:10.1016/j.cell.2011.09.024

    CAS  PubMed Central  PubMed  Google Scholar 

  227. Chiang AC, Massague J (2008) Molecular basis of metastasis. N Engl J Med 359(26):2814–2823. doi:359/26/2814 [pii] 10.1056/NEJMra0805239

    CAS  PubMed  Google Scholar 

  228. Hay ED (1995) An overview of epithelio-mesenchymal transformation. Acta Anat (Basel) 154(1):8–20

    CAS  Google Scholar 

  229. Kalluri R, Neilson EG (2003) Epithelial-mesenchymal transition and its implications for fibrosis. J Clin Invest 112(12):1776–1784. doi:10.1172/JCI20530 112/12/1776 [pii]

    CAS  PubMed Central  PubMed  Google Scholar 

  230. Kalluri R, Weinberg RA (2009) The basics of epithelial-mesenchymal transition. J Clin Invest 119(6):1420–1428. doi:10.1172/JCI3910439104 [pii]

    CAS  PubMed Central  PubMed  Google Scholar 

  231. Radisky DC (2005) Epithelial-mesenchymal transition. J Cell Sci 118(Pt 19):4325–4326. doi:118/19/4325 [pii] 10.1242/jcs.02552

    CAS  PubMed  Google Scholar 

  232. Yang J, Weinberg RA (2008) Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Dev Cell 14(6):818–829. doi:10.1016/j.devcel.2008.05.009

    CAS  PubMed  Google Scholar 

  233. Medici D, Hay ED, Olsen BR (2008) Snail and slug promote epithelial-mesenchymal transition through beta-catenin-T-cell factor-4-dependent expression of transforming growth factor-beta3. Mol Biol Cell 19(11):4875–4887. doi:10.1091/mbc.E08-05-0506

    CAS  PubMed Central  PubMed  Google Scholar 

  234. Hirohashi S (1998) Inactivation of the E-cadherin-mediated cell adhesion system in human cancers. Am J Pathol 153(2):333–339. doi:10.1016/S0002-9440(10)65575-7

    CAS  PubMed  Google Scholar 

  235. Zavadil J, Narasimhan M, Blumenberg M, Schneider RJ (2007) Transforming growth factor-beta and microRNA:mRNA regulatory networks in epithelial plasticity. Cells Tissues Organs 185(1–3):157–161. doi:10.1159/000101316

    CAS  PubMed  Google Scholar 

  236. Gupta GP, Massague J (2006) Cancer metastasis: building a framework. Cell 127(4):679–695. doi:10.1016/j.cell.2006.11.001

    CAS  PubMed  Google Scholar 

  237. Carmeliet P, Jain RK (2011) Principles and mechanisms of vessel normalization for cancer and other angiogenic diseases. Nat Rev Drug Discov 10(6):417–427. doi:10.1038/nrd3455

    CAS  PubMed  Google Scholar 

  238. Joyce JA, Pollard JW (2009) Microenvironmental regulation of metastasis. Nat Rev Cancer 9(4):239–252. doi:10.1038/nrc2618

    CAS  PubMed Central  PubMed  Google Scholar 

  239. Psaila B, Lyden D (2009) The metastatic niche: adapting the foreign soil. Nat Rev Cancer 9(4):285–293. doi:10.1038/nrc2621

    CAS  PubMed Central  PubMed  Google Scholar 

  240. Paget S (1889) The distribution of secondary growths in cancer of the breast. Lancet 133(3421):571–573. doi:10.1016/s0140-6736(00)49915-0

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Carol S. Lim .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Okal, A., Reaz, S., Lim, C.S. (2013). Cancer Biology: Some Causes for a Variety of Different Diseases. In: Bae, Y., Mrsny, R., Park, K. (eds) Cancer Targeted Drug Delivery. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7876-8_5

Download citation

Publish with us

Policies and ethics