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Molecular Carcinogenesis in Gynecologic Neoplasias

  • Elisabeth SmolleEmail author
Chapter
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Abstract

Breast cancer is the most common cancer in women worldwide and accounted for 1.7 million new cases in 2012, which is a quarter of all new cases of cancer. In 2014, the American Cancer Society reported 235,030 new cases of breast cancer and 40,430 deaths related to breast cancer. Among women in the United States, breast cancer is the most common malignancy, the second most common cause of death from cancer and a leading cause of premature mortality from cancer in women. Ovarian cancer occurs with a lifetime risk of 1.4% in the general female population, but with a risk of 15–56% in women carrying a germline mutation of the BRCA1 and BRCA2 genes. Epithelial ovarian cancer (EOC) is the leading cause of death among gynecologic cancers in the western world and the fifth leading cause of cancer-related death in women. Worldwide, about 200,000 women are newly diagnosed, with 125,000 disease-related deaths every year. Endometrial cancer is the most common gynecologic cancer in the USA, accounting for 40,100 new cases and 7470 deaths per year. Endometrial cancer shares similar patterns of distribution by age and geography with ovarian cancer.

Overall gynecologic malignancies pose a significant disease burden, and novel therapeutic strategies are needed to decrease morbidity and mortality from gynecological cancer. Understanding the molecular characteristics of gynecological cancer ist crucial to develop new targeted therapies.

Keywords

Ovarian Cancer Cervical Cancer Endometrial Cancer Epithelial Ovarian Cancer Ovarian Cancer Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Ferlay J, Soerjomataram I, Ervik M, Bray FD. International Agency for Research on Cancer; GLOBOCAN 2012: Cancer Incidence, Mortality and Prevalence Worldwide. http://www.globocan.iarc.fr/pages/fact_sheets_cancer.aspx. Accessed 21 Mar 2014.
  2. 2.
    Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64(1):9–29.PubMedCrossRefGoogle Scholar
  3. 3.
    Howlander N, Noone A, Krapcho M, et al. SEER cancer statistics review, 1975–2012. Bethesda: National Cancer Institute; 2015.Google Scholar
  4. 4.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7–30.PubMedCrossRefGoogle Scholar
  5. 5.
    Bougie O, Weberpals JI. Clinical considerations of BRCA1- and BRCA2-mutation carriers: a review. Int J Surg Oncol. 2011;2011:374012.PubMedPubMedCentralGoogle Scholar
  6. 6.
    King MC, Marks JH, Mandell JB, New York Breast Cancer Study Group. Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science. 2003;302(5645):643–6.PubMedCrossRefGoogle Scholar
  7. 7.
    National Cancer Institute, DCCPS, Surveillance Research Program, Surveillance Systems Branch. Surveillance, Epidemiology, and End Results (SEER) Program. Research Data (1973–2009). Released April 2012 based on November 2011 submission. www.seer.cancer.gov.
  8. 8.
    DeSantis CE, Lin CC, Mariotto AB, Siegel RL, Stein KD, Kramer JL, et al. Cancer treatment and survivorship statistics, 2014. CA Cancer J Clin. 2014;64(4):252–71.PubMedCrossRefGoogle Scholar
  9. 9.
    Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74–108.PubMedCrossRefGoogle Scholar
  10. 10.
    Johnatty SE, Beesley J, Paul J, Fereday S, Spurdle AB, Webb PM, et al. ABCB1 (MDR 1) polymorphisms and progression-free survival among women with ovarian cancer following paclitaxel/carboplatin chemotherapy. Clin Cancer Res. 2008;14(17):5594–601.PubMedCrossRefGoogle Scholar
  11. 11.
    Deraco M, Baratti D, Laterza B, Balestra MR, Mingrone E, Macri A, et al. Advanced cytoreduction as surgical standard of care and hyperthermic intraperitoneal chemotherapy as promising treatment in epithelial ovarian cancer. Eur J Surg Oncol. 2011;37(1):4–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Li J, Fadare O, Xiang L, Kong B, Zheng W. Ovarian serous carcinoma: recent concepts on its origin and carcinogenesis. J Hematol Oncol. 2012;5:8. doi: 10.1186/1756-8722-5-8.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Marquez RT, Baggerly KA, Patterson AP, Liu J, Broaddus R, Frumovitz M, et al. Patterns of gene expression in different histotypes of epithelial ovarian cancer correlate with those in normal fallopian tube, endometrium, and colon. Clin Cancer Res. 2005;11(17):6116–26.PubMedCrossRefGoogle Scholar
  14. 14.
    Bell DA. Origins and molecular pathology of ovarian cancer. Mod Pathol. 2005;18(Suppl 2):S19–32.PubMedCrossRefGoogle Scholar
  15. 15.
    Lacey Jr JV, Mink PJ, Lubin JH, Sherman ME, Troisi R, Hartge P, et al. Menopausal hormone replacement therapy and risk of ovarian cancer. JAMA. 2002;288(3):334–41.PubMedCrossRefGoogle Scholar
  16. 16.
    American Career Society. Cancer facts and figures 2008. 2008.Google Scholar
  17. 17.
    Merritt MA, Cramer DW. Molecular pathogenesis of endometrial and ovarian cancer. Cancer Biomark. 2010;9(1–6):287–305.PubMedGoogle Scholar
  18. 18.
    Parazzini F, Franceschi S, La Vecchia C, Fasoli M. The epidemiology of ovarian cancer. Gynecol Oncol. 1991;43(1):9–23.PubMedCrossRefGoogle Scholar
  19. 19.
    Parazzini F, La Vecchia C, Bocciolone L, Franceschi S. The epidemiology of endometrial cancer. Gynecol Oncol. 1991;41(1):1–16.PubMedCrossRefGoogle Scholar
  20. 20.
    Prentice RL, Thomson CA, Caan B, Hubbell FA, Anderson GL, Beresford SA, et al. Low-fat dietary pattern and cancer incidence in the Women’s Health Initiative Dietary Modification Randomized Controlled Trial. J Natl Cancer Inst. 2007;99(20):1534–43.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Punt S, Thijssen VL, Vrolijk J, de Kroon CD, Gorter A, Jordanova ES. Galectin-1, -3 and -9 expression and clinical significance in squamous cervical cancer. PLoS One. 2015;10(6):e0129119.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Curado MP, Edwards B, Shin HR, Storm H, Ferlay J, Heanue M. Cancer incidence in five continents. IX ed. IARC Scientific Publications No. 160. Lyon: International Agency for Research on Cancer; 2007.Google Scholar
  23. 23.
    Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999;189(1):12–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Bansal N, Herzog TJ, Shaw RE, Burke WM, Deutsch I, Wright JD. Primary therapy for early-stage cervical cancer: radical hysterectomy vs radiation. Am J Obstet Gynecol. 2009;201(5):485.e1–9.CrossRefGoogle Scholar
  25. 25.
    SEER data for 2000–2004. http://seer.cancer.gov/. Accessed 25 April 2011.
  26. 26.
    Ries LAG, Harkins D, Krapcho M, et al. SEER cancer statistics review, 1975 to 2003. Bethesda: National Cancer Institute; 2006.Google Scholar
  27. 27.
    Di Saia PJ, Creasman WT, Mannel RS, McMeekin DS, Mutch DG. Invasive cervical cancer. In: Di Saia PJ, Creasman WT, editors. Clinical gynecologic oncology. 8th ed. Philadelphia: Elsevier; 2012. p. 51–119.Google Scholar
  28. 28.
    Estape R, Angioli R. Surgical management of advanced and recurrent cervical cancer. Semin Surg Oncol. 1999;16(3):236–41.PubMedCrossRefGoogle Scholar
  29. 29.
    Jobsen JJ, Leer JW, Cleton FJ, Hermans J. Treatment of locoregional recurrence of carcinoma of the cervix by radiotherapy after primary surgery. Gynecol Oncol. 1989;33(3):368–71.PubMedCrossRefGoogle Scholar
  30. 30.
    Davis NM, Sokolosky M, Stadelman K, Abrams SL, Libra M, Candido S, et al. Deregulation of the EGFR/PI3K/PTEN/Akt/mTORC1 pathway in breast cancer: possibilities for therapeutic intervention. Oncotarget. 2014;5(13):4603–50.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Yuan TL, Cantley LC. PI3K pathway alterations in cancer: variations on a theme. Oncogene. 2008;27(41):5497–510.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Weigelt B, Warne PH, Downward J. PIK3CA mutation, but not PTEN loss of function, determines the sensitivity of breast cancer cells to mTOR inhibitory drugs. Oncogene. 2011;30(29):3222–33.PubMedCrossRefGoogle Scholar
  33. 33.
    Wheler JJ, Moulder SL, Naing A, Janku F, Piha-Paul SA, Falchook GS, et al. Anastrozole and everolimus in advanced gynecologic and breast malignancies: activity and molecular alterations in the PI3K/AKT/mTOR pathway. Oncotarget. 2014;5(10):3029–38.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Stambolic V. Cancer: precise control of localized signals. Nature. 2015;522(7554):38–40.PubMedCrossRefGoogle Scholar
  35. 35.
    Tashiro H, Blazes MS, Wu R, Cho KR, Bose S, Wang SI, et al. Mutations in PTEN are frequent in endometrial carcinoma but rare in other common gynecological malignancies. Cancer Res. 1997;57(18):3935–40.PubMedGoogle Scholar
  36. 36.
    Mutter GL, Lin MC, Fitzgerald JT, Kum JB, Baak JP, Lees JA, et al. Altered PTEN expression as a diagnostic marker for the earliest endometrial precancers. J Natl Cancer Inst. 2000;92(11):924–30.PubMedCrossRefGoogle Scholar
  37. 37.
    Dinkelspiel HE, Wright JD, Lewin SN, Herzog TJ. Contemporary clinical management of endometrial cancer. Obstet Gynecol Int. 2013;2013:583891.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Di Cristofano A, Pandolfi PP. The multiple roles of PTEN in tumor suppression. Cell. 2000;100(4):387–90.PubMedCrossRefGoogle Scholar
  39. 39.
    Hsu CP, Kao TY, Chang WL, Nieh S, Wang HL, Chung YC. Clinical significance of tumor suppressor PTEN in colorectal carcinoma. Eur J Surg Oncol. 2011;37(2):140–7.PubMedCrossRefGoogle Scholar
  40. 40.
    Pan J, Cheng L, Bi X, Zhang X, Liu S, Bai X, et al. Elevation of omega-3 polyunsaturated fatty acids attenuates PTEN-deficiency induced endometrial cancer development through regulation of COX-2 and PGE2 production. Sci Rep. 2015;5:14958.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Cully M, You H, Levine AJ, Mak TW. Beyond PTEN mutations: the PI3K pathway as an integrator of multiple inputs during tumorigenesis. Nat Rev Cancer. 2006;6(3):184–92.PubMedCrossRefGoogle Scholar
  42. 42.
    Adams JR, Schachter NF, Liu JC, Zacksenhaus E, Egan SE. Elevated PI3K signaling drives multiple breast cancer subtypes. Oncotarget. 2011;2(6):435–47.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Liu JC, Wang DY, Egan SE, Zacksenhaus E. Common and distinct features of mammary tumors driven by Pten-deletion or activating Pik3ca mutation. Oncotarget. 2016;7:9060–8.PubMedPubMedCentralGoogle Scholar
  44. 44.
    Hopkins BD, Fine B, Steinbach N, Dendy M, Rapp Z, Shaw J, et al. A secreted PTEN phosphatase that enters cells to alter signaling and survival. Science. 2013;341(6144):399–402.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Bassi C, Ho J, Srikumar T, Dowling RJ, Gorrini C, Miller SJ, et al. Nuclear PTEN controls DNA repair and sensitivity to genotoxic stress. Science. 2013;341(6144):395–9.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Song MS, Carracedo A, Salmena L, Song SJ, Egia A, Malumbres M, et al. Nuclear PTEN regulates the APC-CDH1 tumor-suppressive complex in a phosphatase-independent manner. Cell. 2011;144(2):187–99.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Song MS, Salmena L, Pandolfi PP. The functions and regulation of the PTEN tumour suppressor. Nat Rev Mol Cell Biol. 2012;13(5):283–96.PubMedGoogle Scholar
  48. 48.
    Zhang S, Huang WC, Li P, Guo H, Poh SB, Brady SW, et al. Combating trastuzumab resistance by targeting SRC, a common node downstream of multiple resistance pathways. Nat Med. 2011;17(4):461–9.PubMedCrossRefGoogle Scholar
  49. 49.
    Shi Y, Wang J, Chandarlapaty S, Cross J, Thompson C, Rosen N, et al. PTEN is a protein tyrosine phosphatase for IRS1. Nat Struct Mol Biol. 2014;21(6):522–7.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Wang S, Liu JC, Kim D, Datti A, Zacksenhaus E. Targeted Pten deletion plus p53-R270H mutation in mouse mammary epithelium induces aggressive claudin-low and basal-like breast cancer. Breast Cancer Res. 2016;18(1):9. doi: 10.1186/s13058-015-0668-y.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Guo L, Wu H, Zhu J, Zhang C, Ma J, Lan J, et al. Genetic variations in the PI3K/AKT pathway predict platinum-based neoadjuvant chemotherapeutic sensitivity in squamous cervical cancer. Life Sci. 2015;143:217–24.PubMedCrossRefGoogle Scholar
  52. 52.
    Du J, Wang L, Li C, Yang H, Li Y, Hu H, et al. MicroRNA-221 targets PTEN to reduce the sensitivity of cervical cancer cells to gefitinib through the PI3K/Akt signaling pathway. Tumour Biol. 2016;37:3939–47.PubMedCrossRefGoogle Scholar
  53. 53.
    Yang YK, Xi WY, Xi RX, Li JY, Li Q, Gao YE. MicroRNA-494 promotes cervical cancer proliferation through the regulation of PTEN. Oncol Rep. 2015 May;33(5):2393–401.PubMedGoogle Scholar
  54. 54.
    Moreno-Bueno G, Gamallo C, Perez-Gallego L, de Mora JC, Suarez A, Palacios J. beta-Catenin expression pattern, beta-catenin gene mutations, and microsatellite instability in endometrioid ovarian carcinomas and synchronous endometrial carcinomas. Diagn Mol Pathol. 2001;10(2):116–22.PubMedCrossRefGoogle Scholar
  55. 55.
    Wu R, Zhai Y, Fearon ER, Cho KR. Diverse mechanisms of beta-catenin deregulation in ovarian endometrioid adenocarcinomas. Cancer Res. 2001;61(22):8247–55.PubMedGoogle Scholar
  56. 56.
    Obata K, Morland SJ, Watson RH, Hitchcock A, Chenevix-Trench G, Thomas EJ, et al. Frequent PTEN/MMAC mutations in endometrioid but not serous or mucinous epithelial ovarian tumors. Cancer Res. 1998;58(10):2095–7.PubMedGoogle Scholar
  57. 57.
    Shih I, Kurman RJ. Ovarian tumorigenesis: a proposed model based on morphological and molecular genetic analysis. Am J Pathol. 2004;164(5):1511–8.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Sato N, Tsunoda H, Nishida M, Morishita Y, Takimoto Y, Kubo T, et al. Loss of heterozygosity on 10q23.3 and mutation of the tumor suppressor gene PTEN in benign endometrial cyst of the ovary: possible sequence progression from benign endometrial cyst to endometrioid carcinoma and clear cell carcinoma of the ovary. Cancer Res. 2000;60(24):7052–6.PubMedGoogle Scholar
  59. 59.
    Hashiguchi Y, Tsuda H, Inoue T, Berkowitz RS, Mok SC. PTEN expression in clear cell adenocarcinoma of the ovary. Gynecol Oncol. 2006;101(1):71–5.PubMedCrossRefGoogle Scholar
  60. 60.
    Folgueira MA, Maistro S, Katayama ML, Roela RA, Mundim FG, Nanogaki S, et al. Markers of breast cancer stromal fibroblasts in the primary tumour site associated with lymph node metastasis: a systematic review including our case series. Biosci Rep. 2013;33(6) doi: 10.1042/BSR20130060.
  61. 61.
    Zhang B, Cao X, Liu Y, Cao W, Zhang F, Zhang S, et al. Tumor-derived matrix metalloproteinase-13 (MMP-13) correlates with poor prognoses of invasive breast cancer. BMC Cancer. 2008;8:83. doi: 10.1186/1471-2407-8-83.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Jung EJ, Moon HG, Cho BI, Jeong CY, Joo YT, Lee YJ, et al. Galectin-1 expression in cancer-associated stromal cells correlates tumor invasiveness and tumor progression in breast cancer. Int J Cancer. 2007;120(11):2331–8.PubMedCrossRefGoogle Scholar
  63. 63.
    Yeung TL, Leung CS, Li F, Wong SS, Mok SC. Targeting Stromal-Cancer Cell Crosstalk Networks in Ovarian Cancer Treatment. Biomolecules. 2016;6(1) doi: 10.3390/biom6010003.
  64. 64.
    Lawrenson K, Grun B, Lee N, Mhawech-Fauceglia P, Kan J, Swenson S, et al. NPPB is a novel candidate biomarker expressed by cancer-associated fibroblasts in epithelial ovarian cancer. Int J Cancer. 2015;136(6):1390–401.PubMedCrossRefGoogle Scholar
  65. 65.
    Yeung TL, Leung CS, Mok SC. CAF reprogramming inhibits ovarian cancer progression. Cell Cycle. 2014;13(24):3783–4.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Yeung TL, Leung CS, Wong KK, Samimi G, Thompson MS, Liu J, et al. TGF-beta modulates ovarian cancer invasion by upregulating CAF-derived versican in the tumor microenvironment. Cancer Res. 2013;73(16):5016–28.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Serini G, Gabbiani G. Mechanisms of myofibroblast activity and phenotypic modulation. Exp Cell Res. 1999;250(2):273–83.PubMedCrossRefGoogle Scholar
  68. 68.
    Erez N, Glanz S, Raz Y, Avivi C, Barshack I. Cancer associated fibroblasts express pro-inflammatory factors in human breast and ovarian tumors. Biochem Biophys Res Commun. 2013;437(3):397–402.PubMedCrossRefGoogle Scholar
  69. 69.
    Mueller MM, Fusenig NE. Friends or foes—bipolar effects of the tumour stroma in cancer. Nat Rev Cancer. 2004;4(11):839–49.PubMedCrossRefGoogle Scholar
  70. 70.
    Chen H, Yang WW, Wen QT, Xu L, Chen M. TGF-beta induces fibroblast activation protein expression; fibroblast activation protein expression increases the proliferation, adhesion, and migration of HO-8910PM [corrected]. Exp Mol Pathol. 2009;87(3):189–94.PubMedCrossRefGoogle Scholar
  71. 71.
    Yang W, Han W, Ye S, Liu D, Wu J, Liu H, et al. Fibroblast activation protein-alpha promotes ovarian cancer cell proliferation and invasion via extracellular and intracellular signaling mechanisms. Exp Mol Pathol. 2013;95(1):105–10.PubMedCrossRefGoogle Scholar
  72. 72.
    Ohira S, Itatsu K, Sasaki M, Harada K, Sato Y, Zen Y, et al. Local balance of transforming growth factor-beta1 secreted from cholangiocarcinoma cells and stromal-derived factor-1 secreted from stromal fibroblasts is a factor involved in invasion of cholangiocarcinoma. Pathol Int. 2006;56(7):381–9.PubMedCrossRefGoogle Scholar
  73. 73.
    Ohira S, Sasaki M, Harada K, Sato Y, Zen Y, Isse K, et al. Possible regulation of migration of intrahepatic cholangiocarcinoma cells by interaction of CXCR4 expressed in carcinoma cells with tumor necrosis factor-alpha and stromal-derived factor-1 released in stroma. Am J Pathol. 2006;168(4):1155–68.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Chang SC, Lin PC, Yang SH, Wang HS, Li AF, Lin JK. SDF-1alpha G801A polymorphism predicts lymph node metastasis in stage T3 colorectal cancer. Ann Surg Oncol. 2009;16(8):2323–30.PubMedCrossRefGoogle Scholar
  75. 75.
    Daly AJ, McIlreavey L, Irwin CR. Regulation of HGF and SDF-1 expression by oral fibroblasts—implications for invasion of oral cancer. Oral Oncol. 2008;44(7):646–51.PubMedCrossRefGoogle Scholar
  76. 76.
    Matsuo Y, Ochi N, Sawai H, Yasuda A, Takahashi H, Funahashi H, et al. CXCL8/IL-8 and CXCL12/SDF-1alpha co-operatively promote invasiveness and angiogenesis in pancreatic cancer. Int J Cancer. 2009;124(4):853–61.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Lau TS, Chung TK, Cheung TH, Chan LK, Cheung LW, Yim SF, et al. Cancer cell-derived lymphotoxin mediates reciprocal tumour-stromal interactions in human ovarian cancer by inducing CXCL11 in fibroblasts. J Pathol. 2014;232(1):43–56.PubMedCrossRefGoogle Scholar
  78. 78.
    McAndrews KM, Yi J, McGrail DJ, Dawson MR. Enhanced adhesion of stromal cells to invasive cancer cells regulated by cadherin 11. ACS Chem Biol. 2015;10(8):1932–8.PubMedCrossRefGoogle Scholar
  79. 79.
    Moran-Jones K, Gloss BS, Murali R, Chang DK, Colvin EK, Jones MD, et al. Connective tissue growth factor as a novel therapeutic target in high grade serous ovarian cancer. Oncotarget. 2015;6:44551–62.PubMedPubMedCentralGoogle Scholar
  80. 80.
    Huang R, Wu D, Yuan Y, Li X, Holm R, Trope CG, et al. CD117 expression in fibroblasts-like stromal cells indicates unfavorable clinical outcomes in ovarian carcinoma patients. PLoS One. 2014;9(11):e112209.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Chen L, Yao Y, Sun L, Zhou J, Liu J, Wang J, et al. Clinical implication of the serum galectin-1 expression in epithelial ovarian cancer patients. J Ovarian Res. 2015;8(1):78. doi: 10.1186/s13048-015-0206-7.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Barondes SH, Castronovo V, Cooper DN, Cummings RD, Drickamer K, Feizi T, et al. Galectins: a family of animal beta-galactoside-binding lectins. Cell. 1994;76(4):597–8.PubMedCrossRefGoogle Scholar
  83. 83.
    Barondes SH, Cooper DN, Gitt MA, Leffler H. Galectins. Structure and function of a large family of animal lectins. J Biol Chem. 1994;269(33):20807–10.PubMedGoogle Scholar
  84. 84.
    Camby I, Le Mercier M, Lefranc F, Kiss R. Galectin-1: a small protein with major functions. Glycobiology. 2006;16(11):137R–57R.PubMedCrossRefGoogle Scholar
  85. 85.
    Liu FT, Rabinovich GA. Galectins as modulators of tumour progression. Nat Rev Cancer. 2005;5(1):29–41.PubMedCrossRefGoogle Scholar
  86. 86.
    Wu MH, Hong TM, Cheng HW, Pan SH, Liang YR, Hong HC, et al. Galectin-1-mediated tumor invasion and metastasis, up-regulated matrix metalloproteinase expression, and reorganized actin cytoskeletons. Mol Cancer Res. 2009;7(3):311–8.PubMedCrossRefGoogle Scholar
  87. 87.
    Thijssen VL, Poirier F, Baum LG, Griffioen AW. Galectins in the tumor endothelium: opportunities for combined cancer therapy. Blood. 2007;110(8):2819–27.PubMedCrossRefGoogle Scholar
  88. 88.
    Thijssen VL, Postel R, Brandwijk RJ, Dings RP, Nesmelova I, Satijn S, et al. Galectin-1 is essential in tumor angiogenesis and is a target for antiangiogenesis therapy. Proc Natl Acad Sci U S A. 2006;103(43):15975–80.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Rabinovich GA, Ilarregui JM. Conveying glycan information into T-cell homeostatic programs: a challenging role for galectin-1 in inflammatory and tumor microenvironments. Immunol Rev. 2009;230(1):144–59.PubMedCrossRefGoogle Scholar
  90. 90.
    Kovacs-Solyom F, Blasko A, Fajka-Boja R, Katona RL, Vegh L, Novak J, et al. Mechanism of tumor cell-induced T-cell apoptosis mediated by galectin-1. Immunol Lett. 2010;127(2):108–18.PubMedCrossRefGoogle Scholar
  91. 91.
    Xu XC, el-Naggar AK, Lotan R. Differential expression of galectin-1 and galectin-3 in thyroid tumors. Potential diagnostic implications. Am J Pathol. 1995;147(3):815–22.PubMedPubMedCentralGoogle Scholar
  92. 92.
    Chiariotti L, Berlingieri MT, Battaglia C, Benvenuto G, Martelli ML, Salvatore P, et al. Expression of galectin-1 in normal human thyroid gland and in differentiated and poorly differentiated thyroid tumors. Int J Cancer. 1995;64(3):171–5.PubMedCrossRefGoogle Scholar
  93. 93.
    Wu MH, Hong HC, Hong TM, Chiang WF, Jin YT, Chen YL. Targeting galectin-1 in carcinoma-associated fibroblasts inhibits oral squamous cell carcinoma metastasis by downregulating MCP-1/CCL2 expression. Clin Cancer Res. 2011;17(6):1306–16.PubMedCrossRefGoogle Scholar
  94. 94.
    van den Brule F, Califice S, Garnier F, Fernandez PL, Berchuck A, Castronovo V. Galectin-1 accumulation in the ovary carcinoma peritumoral stroma is induced by ovary carcinoma cells and affects both cancer cell proliferation and adhesion to laminin-1 and fibronectin. Lab Invest. 2003;83(3):377–86.PubMedCrossRefGoogle Scholar
  95. 95.
    Kim HJ, Jeon HK, Cho YJ, Park YA, Choi JJ, Do IG, et al. High galectin-1 expression correlates with poor prognosis and is involved in epithelial ovarian cancer proliferation and invasion. Eur J Cancer. 2012;48(12):1914–21.PubMedCrossRefGoogle Scholar
  96. 96.
    Zhang P, Zhang P, Shi B, Zhou M, Jiang H, Zhang H, et al. Galectin-1 overexpression promotes progression and chemoresistance to cisplatin in epithelial ovarian cancer. Cell Death Dis. 2014;5:e991.PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Huang EY, Chanchien CC, Lin H, Wang CC, Wang CJ, Huang CC. Galectin-1 is an independent prognostic factor for local recurrence and survival after definitive radiation therapy for patients with squamous cell carcinoma of the uterine cervix. Int J Radiat Oncol Biol Phys. 2013;87(5):975–82.PubMedCrossRefGoogle Scholar
  98. 98.
    Benes P, Vetvicka V, Fusek M. Cathepsin D—many functions of one aspartic protease. Crit Rev Oncol Hematol. 2008;68(1):12–28.PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Pranjol MZ, Gutowski N, Hannemann M, Whatmore J. The potential role of the proteases cathepsin D and cathepsin L in the progression and metastasis of epithelial ovarian cancer. Biomolecules. 2015;5(4):3260–79.PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Mathieu M, Vignon F, Capony F, Rochefort H. Estradiol down-regulates the mannose-6-phosphate/insulin-like growth factor-II receptor gene and induces cathepsin-D in breast cancer cells: a receptor saturation mechanism to increase the secretion of lysosomal proenzymes. Mol Endocrinol. 1991;5(6):815–22.PubMedCrossRefGoogle Scholar
  101. 101.
    Kagedal K, Johansson U, Ollinger K. The lysosomal protease cathepsin D mediates apoptosis induced by oxidative stress. FASEB J. 2001;15(9):1592–4.PubMedGoogle Scholar
  102. 102.
    Heinrich M, Neumeyer J, Jakob M, Hallas C, Tchikov V, Winoto-Morbach S, et al. Cathepsin D links TNF-induced acid sphingomyelinase to Bid-mediated caspase-9 and -3 activation. Cell Death Differ. 2004;11(5):550–63.PubMedCrossRefGoogle Scholar
  103. 103.
    Blomgran R, Zheng L, Stendahl O. Cathepsin-cleaved Bid promotes apoptosis in human neutrophils via oxidative stress-induced lysosomal membrane permeabilization. J Leukoc Biol. 2007;81(5):1213–23.PubMedCrossRefGoogle Scholar
  104. 104.
    Zuzarte-Luis V, Montero JA, Kawakami Y, Izpisua-Belmonte JC, Hurle JM. Lysosomal cathepsins in embryonic programmed cell death. Dev Biol. 2007;301(1):205–17.PubMedCrossRefGoogle Scholar
  105. 105.
    Zuzarte-Luis V, Montero JA, Torre-Perez N, Garcia-Porrero JA, Hurle JM. Cathepsin D gene expression outlines the areas of physiological cell death during embryonic development. Dev Dyn. 2007;236(3):880–5.PubMedCrossRefGoogle Scholar
  106. 106.
    Ohri SS, Vashishta A, Proctor M, Fusek M, Vetvicka V. The propeptide of cathepsin D increases proliferation, invasion and metastasis of breast cancer cells. Int J Oncol. 2008;32(2):491–8.PubMedGoogle Scholar
  107. 107.
    Winiarski BK, Wolanska KI, Rai S, Ahmed T, Acheson N, Gutowski NJ, et al. Epithelial ovarian cancer-induced angiogenic phenotype of human omental microvascular endothelial cells may occur independently of VEGF signaling. Transl Oncol. 2013;6(6):703–14.PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Rochefort H. Cathepsin D in breast cancer: a tissue marker associated with metastasis. Eur J Cancer. 1992;28A(11):1780–3.PubMedCrossRefGoogle Scholar
  109. 109.
    Rochefort H, Garcia M, Glondu M, Laurent V, Liaudet E, Rey JM, et al. Cathepsin D in breast cancer: mechanisms and clinical applications, a 1999 overview. Clin Chim Acta. 2000;291(2):157–70.PubMedCrossRefGoogle Scholar
  110. 110.
    Ferrandina G, Scambia G, Bardelli F, Benedetti Panici P, Mancuso S, Messori A. Relationship between cathepsin-D content and disease-free survival in node-negative breast cancer patients: a meta-analysis. Br J Cancer. 1997;76(5):661–6.PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    Foekens JA, Look MP, Bolt-de Vries J, Meijer-van Gelder ME, van Putten WL, Klijn JG. Cathepsin-D in primary breast cancer: prognostic evaluation involving 2810 patients. Br J Cancer. 1999;79(2):300–7.PubMedPubMedCentralCrossRefGoogle Scholar
  112. 112.
    Briozzo P, Badet J, Capony F, Pieri I, Montcourrier P, Barritault D, et al. MCF7 mammary cancer cells respond to bFGF and internalize it following its release from extracellular matrix: a permissive role of cathepsin D. Exp Cell Res. 1991;194(2):252–9.PubMedCrossRefGoogle Scholar
  113. 113.
    Losch A, Kohlberger P, Gitsch G, Kaider A, Breitenecker G, Kainz C. Lysosomal protease cathepsin D is a prognostic marker in endometrial cancer. Br J Cancer. 1996;73(12):1525–8.PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Nazeer T, Malfetano JH, Rosano TG, Ross JS. Correlation of tumor cytosol cathepsin D with differentiation and invasiveness of endometrial adenocarcinoma. Am J Clin Pathol. 1992;97(6):764–9.PubMedCrossRefGoogle Scholar
  115. 115.
    Henzen-Logmans SC, Fieret EJ, Berns EM, van der Burg ME, Klijn JG, Foekens JA. Ki-67 staining in benign, borderline, malignant primary and metastatic ovarian tumors: correlation with steroid receptors, epidermal-growth-factor receptor and cathepsin D. Int J Cancer. 1994;57(4):468–72.PubMedCrossRefGoogle Scholar
  116. 116.
    Losch A, Schindl M, Kohlberger P, Lahodny J, Breitenecker G, Horvat R, et al. Cathepsin D in ovarian cancer: prognostic value and correlation with p53 expression and microvessel density. Gynecol Oncol. 2004;92(2):545–52.PubMedCrossRefGoogle Scholar
  117. 117.
    Chai Y, Wu W, Zhou C, Zhou J. The potential prognostic value of cathepsin D protein in serous ovarian cancer. Arch Gynecol Obstet. 2012;286(2):465–71.PubMedCrossRefGoogle Scholar
  118. 118.
    Winiarski BK, Cope N, Alexander M, Pilling LC, Warren S, Acheson N, et al. Clinical relevance of increased endothelial and mesothelial expression of proangiogenic proteases and VEGFA in the omentum of patients with metastatic ovarian high-grade serous carcinoma. Transl Oncol. 2014;7(2):267–276.e4.PubMedPubMedCentralCrossRefGoogle Scholar
  119. 119.
    Rochefort H, Capony F, Garcia M, Cavailles V, Freiss G, Chambon M, et al. Estrogen-induced lysosomal proteases secreted by breast cancer cells: a role in carcinogenesis? J Cell Biochem. 1987;35(1):17–29.PubMedCrossRefGoogle Scholar
  120. 120.
    Vignon F, Capony F, Chambon M, Freiss G, Garcia M, Rochefort H. Autocrine growth stimulation of the MCF 7 breast cancer cells by the estrogen-regulated 52K protein. Endocrinology. 1986;118(4):1537–45.PubMedCrossRefGoogle Scholar
  121. 121.
    Kirschke H, Langner J, Wiederanders B, Ansorge S, Bohley P. Cathepsin L. A new proteinase from rat-liver lysosomes. Eur J Biochem. 1977;74(2):293–301.PubMedCrossRefGoogle Scholar
  122. 122.
    Kominami E, Ueno T, Muno D, Katunuma N. The selective role of cathepsins B and D in the lysosomal degradation of endogenous and exogenous proteins. FEBS Lett. 1991;287(1–2):189–92.PubMedCrossRefGoogle Scholar
  123. 123.
    Nguyen Q, Mort JS, Roughley PJ. Cartilage proteoglycan aggregate is degraded more extensively by cathepsin L than by cathepsin B. Biochem J. 1990;266(2):569–73.PubMedPubMedCentralGoogle Scholar
  124. 124.
    Nosaka AY, Kanaori K, Teno N, Togame H, Inaoka T, Takai M, et al. Conformational studies on the specific cleavage site of Type I collagen (alpha-1) fragment (157-192) by cathepsins K and L by proton NMR spectroscopy. Bioorg Med Chem. 1999;7(2):375–9.PubMedCrossRefGoogle Scholar
  125. 125.
    Mason RW, Johnson DA, Barrett AJ, Chapman HA. Elastinolytic activity of human cathepsin L. Biochem J. 1986;233(3):925–7.PubMedPubMedCentralCrossRefGoogle Scholar
  126. 126.
    Ishidoh K, Kominami E. Procathepsin L degrades extracellular matrix proteins in the presence of glycosaminoglycans in vitro. Biochem Biophys Res Commun. 1995;217(2):624–31.PubMedCrossRefGoogle Scholar
  127. 127.
    Maciewicz RA, Wotton SF, Etherington DJ, Duance VC. Susceptibility of the cartilage collagens types II, IX and XI to degradation by the cysteine proteinases, cathepsins B and L. FEBS Lett. 1990;269(1):189–93.PubMedCrossRefGoogle Scholar
  128. 128.
    Maciewicz RA, Wotton SF. Degradation of cartilage matrix components by the cysteine proteinases, cathepsins B and L. Biomed Biochim Acta. 1991;50(4–6):561–4.PubMedGoogle Scholar
  129. 129.
    Nishida Y, Kohno K, Kawamata T, Morimitsu K, Kuwano M, Miyakawa I. Increased cathepsin L levels in serum in some patients with ovarian cancer: comparison with CA125 and CA72-4. Gynecol Oncol. 1995;56(3):357–61.PubMedCrossRefGoogle Scholar
  130. 130.
    Zhang W, Wang S, Wang Q, Yang Z, Pan Z, Li L. Overexpression of cysteine cathepsin L is a marker of invasion and metastasis in ovarian cancer. Oncol Rep. 2014;31(3):1334–42.PubMedGoogle Scholar
  131. 131.
    Zhang L, Wei L, Shen G, He B, Gong W, Min N, et al. Cathepsin L is involved in proliferation and invasion of ovarian cancer cells. Mol Med Rep. 2015;11(1):468–74.PubMedGoogle Scholar
  132. 132.
    Arbyn M, Ronco G, Anttila A, Meijer CJ, Poljak M, Ogilvie G, et al. Evidence regarding human papillomavirus testing in secondary prevention of cervical cancer. Vaccine. 2012;30(Suppl 5):F88–99.PubMedCrossRefGoogle Scholar
  133. 133.
    Carozzi F, Visioli CB, Confortini M, Iossa A, Mantellini P, Burroni E, et al. hr-HPV testing in the follow-up of women with cytological abnormalities and negative colposcopy. Br J Cancer. 2013;109(7):1766–74.PubMedPubMedCentralCrossRefGoogle Scholar
  134. 134.
    Meijer CJ, Berkhof H, Heideman DA, Hesselink AT, Snijders PJ. Validation of high-risk HPV tests for primary cervical screening. J Clin Virol. 2009;46(Suppl 3):S1–4.PubMedCrossRefGoogle Scholar
  135. 135.
    Tornesello ML, Buonaguro L, Giorgi-Rossi P, Buonaguro FM. Viral and cellular biomarkers in the diagnosis of cervical intraepithelial neoplasia and cancer. Biomed Res Int. 2013;2013:519619.PubMedPubMedCentralCrossRefGoogle Scholar
  136. 136.
    Ronco G, Giorgi-Rossi P, Carozzi F, Confortini M, Dalla Palma P, Del Mistro A, et al. Efficacy of human papillomavirus testing for the detection of invasive cervical cancers and cervical intraepithelial neoplasia: a randomised controlled trial. Lancet Oncol. 2010;11(3):249–57.PubMedCrossRefGoogle Scholar
  137. 137.
    Castle PE, Fetterman B, Poitras N, Lorey T, Shaber R, Kinney W. Relationship of atypical glandular cell cytology, age, and human papillomavirus detection to cervical and endometrial cancer risks. Obstet Gynecol. 2010;115(2 Pt 1):243–8.PubMedCrossRefGoogle Scholar
  138. 138.
    Khleif SN, DeGregori J, Yee CL, Otterson GA, Kaye FJ, Nevins JR, et al. Inhibition of cyclin D-CDK4/CDK6 activity is associated with an E2F-mediated induction of cyclin kinase inhibitor activity. Proc Natl Acad Sci U S A. 1996;93(9):4350–4.PubMedPubMedCentralCrossRefGoogle Scholar
  139. 139.
    Nakao Y, Yang X, Yokoyama M, Ferenczy A, Tang SC, Pater MM, et al. Induction of p16 during immortalization by HPV 16 and 18 and not during malignant transformation. Br J Cancer. 1997;75(10):1410–6.PubMedPubMedCentralCrossRefGoogle Scholar
  140. 140.
    Pannone G, Rodolico V, Santoro A, Lo Muzio L, Franco R, Botti G, et al. Evaluation of a combined triple method to detect causative HPV in oral and oropharyngeal squamous cell carcinomas: p16 immunohistochemistry, consensus PCR HPV-DNA, and in situ hybridization. Infect Agent Cancer. 2012;7:4. doi: 10.1186/1750-9378-7-4.PubMedPubMedCentralCrossRefGoogle Scholar
  141. 141.
    Zhang Q, Kuhn L, Denny LA, De Souza M, Taylor S, Wright Jr TC. Impact of utilizing p16INK4A immunohistochemistry on estimated performance of three cervical cancer screening tests. Int J Cancer. 2007;120(2):351–6.PubMedCrossRefGoogle Scholar
  142. 142.
    Roelens J, Reuschenbach M, von Knebel Doeberitz M, Wentzensen N, Bergeron C, Arbyn M. p16INK4a immunocytochemistry versus human papillomavirus testing for triage of women with minor cytologic abnormalities: a systematic review and meta-analysis. Cancer Cytopathol. 2012;120(5):294–307.PubMedPubMedCentralCrossRefGoogle Scholar
  143. 143.
    Reuschenbach M, Seiz M, von Knebel DC, Vinokurova S, Duwe A, Ridder R, et al. Evaluation of cervical cone biopsies for coexpression of p16INK4a and Ki-67 in epithelial cells. Int J Cancer. 2012;130(2):388–94.PubMedCrossRefGoogle Scholar
  144. 144.
    Schmidt D, Bergeron C, Denton KJ, Ridder R, European CINtec Cytology Study Group. p16/ki-67 dual-stain cytology in the triage of ASCUS and LSIL papanicolaou cytology: results from the European equivocal or mildly abnormal papanicolaou cytology study. Cancer Cytopathol. 2011;119(3):158–66.PubMedCrossRefGoogle Scholar
  145. 145.
    Sahasrabuddhe VV, Luhn P, Wentzensen N. Human papillomavirus and cervical cancer: biomarkers for improved prevention efforts. Future Microbiol. 2011;6(9):1083–98.PubMedCrossRefGoogle Scholar
  146. 146.
    Depuydt CE, Makar AP, Ruymbeke MJ, Benoy IH, Vereecken AJ, Bogers JJ. BD-ProExC as adjunct molecular marker for improved detection of CIN2+ after HPV primary screening. Cancer Epidemiol Biomarkers Prev. 2011;20(4):628–37.PubMedCrossRefGoogle Scholar
  147. 147.
    Van Doorslaer K, Burk RD. Association between hTERT activation by HPV E6 proteins and oncogenic risk. Virology. 2012;433(1):216–9.PubMedPubMedCentralCrossRefGoogle Scholar
  148. 148.
    Liu H, Liu S, Wang H, Xie X, Chen X, Zhang X, et al. Genomic amplification of the human telomerase gene (hTERC) associated with human papillomavirus is related to the progression of uterine cervical dysplasia to invasive cancer. Diagn Pathol. 2012;7:147. doi: 10.1186/1746-1596-7-147.PubMedPubMedCentralCrossRefGoogle Scholar
  149. 149.
    Fiorucci G, Chiantore MV, Mangino G, Percario ZA, Affabris E, Romeo G. Cancer regulator microRNA: potential relevance in diagnosis, prognosis and treatment of cancer. Curr Med Chem. 2012;19(4):461–74.PubMedCrossRefGoogle Scholar
  150. 150.
    Gadducci A, Guerrieri ME, Greco C. Tissue biomarkers as prognostic variables of cervical cancer. Crit Rev Oncol Hematol. 2013;86(2):104–29.PubMedCrossRefGoogle Scholar
  151. 151.
    Xu J, Li Y, Wang F, Wang X, Cheng B, Ye F, et al. Suppressed miR-424 expression via upregulation of target gene Chk1 contributes to the progression of cervical cancer. Oncogene. 2013;32(8):976–87.PubMedCrossRefGoogle Scholar
  152. 152.
    Li Y, Liu J, Yuan C, Cui B, Zou X, Qiao Y. High-risk human papillomavirus reduces the expression of microRNA-218 in women with cervical intraepithelial neoplasia. J Int Med Res. 2010;38(5):1730–6.PubMedCrossRefGoogle Scholar
  153. 153.
    Wang F, Li Y, Zhou J, Xu J, Peng C, Ye F, et al. miR-375 is down-regulated in squamous cervical cancer and inhibits cell migration and invasion via targeting transcription factor SP1. Am J Pathol. 2011;179(5):2580–8.PubMedPubMedCentralCrossRefGoogle Scholar
  154. 154.
    Bird A. DNA methylation patterns and epigenetic memory. Genes Dev. 2002;16(1):6–21.PubMedCrossRefGoogle Scholar
  155. 155.
    Sharma S, Kelly TK, Jones PA. Epigenetics in cancer. Carcinogenesis. 2010;31(1):27–36.PubMedCrossRefGoogle Scholar
  156. 156.
    Cuzick J, Bergeron C, von Knebel DM, Gravitt P, Jeronimo J, Lorincz AT, et al. New technologies and procedures for cervical cancer screening. Vaccine. 2012;30(Suppl 5):F107–16.PubMedCrossRefGoogle Scholar
  157. 157.
    Wentzensen N, Sun C, Ghosh A, Kinney W, Mirabello L, Wacholder S, et al. Methylation of HPV18, HPV31, and HPV45 genomes and cervical intraepithelial neoplasia grade 3. J Natl Cancer Inst. 2012;104(22):1738–49.PubMedPubMedCentralCrossRefGoogle Scholar
  158. 158.
    Mirabello L, Sun C, Ghosh A, Rodriguez AC, Schiffman M, Wentzensen N, et al. Methylation of human papillomavirus type 16 genome and risk of cervical precancer in a Costa Rican population. J Natl Cancer Inst. 2012;104(7):556–65.PubMedPubMedCentralCrossRefGoogle Scholar
  159. 159.
    Sova P, Feng Q, Geiss G, Wood T, Strauss R, Rudolf V, et al. Discovery of novel methylation biomarkers in cervical carcinoma by global demethylation and microarray analysis. Cancer Epidemiol Biomarkers Prev. 2006;15(1):114–23.PubMedCrossRefGoogle Scholar
  160. 160.
    Wang SS, Smiraglia DJ, Wu YZ, Ghosh S, Rader JS, Cho KR, et al. Identification of novel methylation markers in cervical cancer using restriction landmark genomic scanning. Cancer Res. 2008;68(7):2489–97.PubMedCrossRefGoogle Scholar
  161. 161.
    Steenbergen RD, Kramer D, Braakhuis BJ, Stern PL, Verheijen RH, Meijer CJ, et al. TSLC1 gene silencing in cervical cancer cell lines and cervical neoplasia. J Natl Cancer Inst. 2004;96(4):294–305.PubMedCrossRefGoogle Scholar
  162. 162.
    Wentzensen N, Sherman ME, Schiffman M, Wang SS. Utility of methylation markers in cervical cancer early detection: appraisal of the state-of-the-science. Gynecol Oncol. 2009;112(2):293–9.PubMedCrossRefGoogle Scholar
  163. 163.
    Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75(5):843–54.PubMedCrossRefGoogle Scholar
  164. 164.
    He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 2004;5(7):522–31.PubMedCrossRefGoogle Scholar
  165. 165.
    Ambros V. microRNAs: tiny regulators with great potential. Cell. 2001;107(7):823–6.PubMedCrossRefGoogle Scholar
  166. 166.
    Forman JJ, Legesse-Miller A, Coller HA. A search for conserved sequences in coding regions reveals that the let-7 microRNA targets Dicer within its coding sequence. Proc Natl Acad Sci U S A. 2008;105(39):14879–84.PubMedPubMedCentralCrossRefGoogle Scholar
  167. 167.
    Lytle JR, Yario TA, Steitz JA. Target mRNAs are repressed as efficiently by microRNA-binding sites in the 5′ UTR as in the 3′ UTR. Proc Natl Acad Sci U S A. 2007;104(23):9667–72.PubMedPubMedCentralCrossRefGoogle Scholar
  168. 168.
    Croce CM. Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet. 2009;10(10):704–14.PubMedPubMedCentralCrossRefGoogle Scholar
  169. 169.
    Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A. 2004;101(9):2999–3004.PubMedPubMedCentralCrossRefGoogle Scholar
  170. 170.
    Melo SA, Moutinho C, Ropero S, Calin GA, Rossi S, Spizzo R, et al. A genetic defect in exportin-5 traps precursor microRNAs in the nucleus of cancer cells. Cancer Cell. 2010;18(4):303–15.PubMedCrossRefGoogle Scholar
  171. 171.
    Helland A, Anglesio MS, George J, Cowin PA, Johnstone CN, House CM, et al. Deregulation of MYCN, LIN28B and LET7 in a molecular subtype of aggressive high-grade serous ovarian cancers. PLoS One. 2011;6(4):e18064.PubMedPubMedCentralCrossRefGoogle Scholar
  172. 172.
    Schrauder MG, Strick R, Schulz-Wendtland R, Strissel PL, Kahmann L, Loehberg CR, et al. Circulating micro-RNAs as potential blood-based markers for early stage breast cancer detection. PLoS One. 2012;7(1):e29770.PubMedPubMedCentralCrossRefGoogle Scholar
  173. 173.
    O’Day E, Lal A. MicroRNAs and their target gene networks in breast cancer. Breast Cancer Res. 2010;12(2):201.PubMedPubMedCentralCrossRefGoogle Scholar
  174. 174.
    Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005;65(16):7065–70.PubMedCrossRefGoogle Scholar
  175. 175.
    Foekens JA, Sieuwerts AM, Smid M, Look MP, de Weerd V, Boersma AW, et al. Four miRNAs associated with aggressiveness of lymph node-negative, estrogen receptor-positive human breast cancer. Proc Natl Acad Sci U S A. 2008;105(35):13021–6.PubMedPubMedCentralCrossRefGoogle Scholar
  176. 176.
    Lowery AJ, Miller N, Devaney A, McNeill RE, Davoren PA, Lemetre C, et al. MicroRNA signatures predict oestrogen receptor, progesterone receptor and HER2/neu receptor status in breast cancer. Breast Cancer Res. 2009;11(3):R27.PubMedPubMedCentralCrossRefGoogle Scholar
  177. 177.
    Kondo N, Toyama T, Sugiura H, Fujii Y, Yamashita H. miR-206 Expression is down-regulated in estrogen receptor alpha-positive human breast cancer. Cancer Res. 2008;68(13):5004–8.PubMedCrossRefGoogle Scholar
  178. 178.
    Blenkiron C, Goldstein LD, Thorne NP, Spiteri I, Chin SF, Dunning MJ, et al. MicroRNA expression profiling of human breast cancer identifies new markers of tumor subtype. Genome Biol. 2007;8(10):R214.PubMedPubMedCentralCrossRefGoogle Scholar
  179. 179.
    Yan LX, Huang XF, Shao Q, Huang MY, Deng L, Wu QL, et al. MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinical stage, lymph node metastasis and patient poor prognosis. RNA. 2008;14(11):2348–60.PubMedPubMedCentralCrossRefGoogle Scholar
  180. 180.
    Van der Auwera I, Limame R, van Dam P, Vermeulen PB, Dirix LY, Van Laere SJ. Integrated miRNA and mRNA expression profiling of the inflammatory breast cancer subtype. Br J Cancer. 2010;103(4):532–41.PubMedPubMedCentralCrossRefGoogle Scholar
  181. 181.
    Cai Y, Yan X, Zhang G, Zhao W, Jiao S. MicroRNA-205 increases the sensitivity of docetaxel in breast cancer. Oncol Lett. 2016;11(2):1105–9.PubMedGoogle Scholar
  182. 182.
    Pal MK, Jaiswar SP, Dwivedi VN, Tripathi AK, Dwivedi A, Sankhwar P. MicroRNA: a new and promising potential biomarker for diagnosis and prognosis of ovarian cancer. Cancer Biol Med. 2015;12(4):328–41.PubMedPubMedCentralGoogle Scholar
  183. 183.
    Chen PS, Su JL, Hung MC. Dysregulation of microRNAs in cancer. J Biomed Sci. 2012;19:90. doi: 10.1186/1423-0127-19-90.PubMedPubMedCentralCrossRefGoogle Scholar
  184. 184.
    Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6(11):857–66.PubMedCrossRefGoogle Scholar
  185. 185.
    Zhang W, Dahlberg JE, Tam W. MicroRNAs in tumorigenesis: a primer. Am J Pathol. 2007;171(3):728–38.PubMedPubMedCentralCrossRefGoogle Scholar
  186. 186.
    Parikh A, Lee C, Joseph P, Marchini S, Baccarini A, Kolev V, et al. microRNA-181a has a critical role in ovarian cancer progression through the regulation of the epithelial-mesenchymal transition. Nat Commun. 2014;5:2977.PubMedPubMedCentralCrossRefGoogle Scholar
  187. 187.
    Wang X, Cao L, Wang Y, Wang X, Liu N, You Y. Regulation of let-7 and its target oncogenes (review). Oncol Lett. 2012;3(5):955–60.PubMedPubMedCentralGoogle Scholar
  188. 188.
    Gregory PA, Bracken CP, Bert AG, Goodall GJ. MicroRNAs as regulators of epithelial-mesenchymal transition. Cell Cycle. 2008;7(20):3112–8.PubMedCrossRefGoogle Scholar
  189. 189.
    Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, et al. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol. 2008;10(5):593–601.PubMedCrossRefGoogle Scholar
  190. 190.
    Park SM, Gaur AB, Lengyel E, Peter ME. The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev. 2008;22(7):894–907.PubMedPubMedCentralCrossRefGoogle Scholar
  191. 191.
    Korpal M, Lee ES, Hu G, Kang Y. The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2. J Biol Chem. 2008;283(22):14910–4.PubMedPubMedCentralCrossRefGoogle Scholar
  192. 192.
    Leskela S, Leandro-Garcia LJ, Mendiola M, Barriuso J, Inglada-Perez L, Munoz I, et al. The miR-200 family controls beta-tubulin III expression and is associated with paclitaxel-based treatment response and progression-free survival in ovarian cancer patients. Endocr Relat Cancer. 2010;18(1):85–95.PubMedCrossRefGoogle Scholar
  193. 193.
    Sun N, Zhang Q, Xu C, Zhao Q, Ma Y, Lu X, et al. Molecular regulation of ovarian cancer cell invasion. Tumour Biol. 2014;35(11):11359–66.PubMedCrossRefGoogle Scholar
  194. 194.
    Kim NH, Kim HS, Li XY, Lee I, Choi HS, Kang SE, et al. A p53/miRNA-34 axis regulates Snail1-dependent cancer cell epithelial-mesenchymal transition. J Cell Biol. 2011;195(3):417–33.PubMedPubMedCentralCrossRefGoogle Scholar
  195. 195.
    Corney DC, Hwang CI, Matoso A, Vogt M, Flesken-Nikitin A, Godwin AK, et al. Frequent downregulation of miR-34 family in human ovarian cancers. Clin Cancer Res. 2010;16(4):1119–28.PubMedPubMedCentralCrossRefGoogle Scholar
  196. 196.
    Mateescu B, Batista L, Cardon M, Gruosso T, de Feraudy Y, Mariani O, et al. miR-141 and miR-200a act on ovarian tumorigenesis by controlling oxidative stress response. Nat Med. 2011;17(12):1627–35.PubMedCrossRefGoogle Scholar
  197. 197.
    Yang H, Kong W, He L, Zhao JJ, O’Donnell JD, Wang J, et al. MicroRNA expression profiling in human ovarian cancer: miR-214 induces cell survival and cisplatin resistance by targeting PTEN. Cancer Res. 2008;68(2):425–33.PubMedCrossRefGoogle Scholar
  198. 198.
    Lou Y, Yang X, Wang F, Cui Z, Huang Y. MicroRNA-21 promotes the cell proliferation, invasion and migration abilities in ovarian epithelial carcinomas through inhibiting the expression of PTEN protein. Int J Mol Med. 2010;26(6):819–27.PubMedCrossRefGoogle Scholar
  199. 199.
    Nagaraja AK, Creighton CJ, Yu Z, Zhu H, Gunaratne PH, Reid JG, et al. A link between mir-100 and FRAP1/mTOR in clear cell ovarian cancer. Mol Endocrinol. 2010;24(2):447–63.PubMedPubMedCentralCrossRefGoogle Scholar
  200. 200.
    Peng DX, Luo M, Qiu LW, He YL, Wang XF. Prognostic implications of microRNA-100 and its functional roles in human epithelial ovarian cancer. Oncol Rep. 2012;27(4):1238–44.PubMedPubMedCentralGoogle Scholar
  201. 201.
    Iorio MV, Visone R, Di Leva G, Donati V, Petrocca F, Casalini P, et al. MicroRNA signatures in human ovarian cancer. Cancer Res. 2007;67(18):8699–707.PubMedCrossRefGoogle Scholar
  202. 202.
    Wyman SK, Parkin RK, Mitchell PS, Fritz BR, O'Briant K, Godwin AK, et al. Repertoire of microRNAs in epithelial ovarian cancer as determined by next generation sequencing of small RNA cDNA libraries. PLoS One. 2009;4(4):e5311.PubMedPubMedCentralCrossRefGoogle Scholar
  203. 203.
    Lee H, Park CS, Deftereos G, Morihara J, Stern JE, Hawes SE, et al. MicroRNA expression in ovarian carcinoma and its correlation with clinicopathological features. World J Surg Oncol. 2012;10:174.PubMedPubMedCentralCrossRefGoogle Scholar
  204. 204.
    Resnick KE, Alder H, Hagan JP, Richardson DL, Croce CM, Cohn DE. The detection of differentially expressed microRNAs from the serum of ovarian cancer patients using a novel real-time PCR platform. Gynecol Oncol. 2009;112(1):55–9.PubMedCrossRefGoogle Scholar
  205. 205.
    Eitan R, Kushnir M, Lithwick-Yanai G, David MB, Hoshen M, Glezerman M, et al. Tumor microRNA expression patterns associated with resistance to platinum based chemotherapy and survival in ovarian cancer patients. Gynecol Oncol. 2009;114(2):253–9.PubMedCrossRefGoogle Scholar
  206. 206.
    Xu YZ, Xi QH, Ge WL, Zhang XQ. Identification of serum microRNA-21 as a biomarker for early detection and prognosis in human epithelial ovarian cancer. Asian Pac J Cancer Prev. 2013;14(2):1057–60.PubMedCrossRefGoogle Scholar
  207. 207.
    Wan WN, Zhang YQ, Wang XM, Liu YJ, Zhang YX, Que YH, et al. Down-regulated miR-22 as predictive biomarkers for prognosis of epithelial ovarian cancer. Diagn Pathol. 2014;9:178. doi: 10.1186/s13000-014-0178-8.PubMedPubMedCentralCrossRefGoogle Scholar
  208. 208.
    Vecchione A, Belletti B, Lovat F, Volinia S, Chiappetta G, Giglio S, et al. A microRNA signature defines chemoresistance in ovarian cancer through modulation of angiogenesis. Proc Natl Acad Sci U S A. 2013;110(24):9845–50.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Department of Internal Medicine, Division of PulmonologyMedical University GrazGrazAustria

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