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What roles do colon stem cells and gap junctions play in the left and right location of origin of colorectal cancers?

  • Commentary
  • Published:
Journal of Cell Communication and Signaling Aims and scope

Abstract

This “Commentary” examines an important clinical observation that right-sided colorectal cancers appear less treatable than the left-sided cancers. The concepts of (a) the “initiation/promotion/progression” process, (b) the stem cell hypothesis, (c) the role gap junctional intercellular communication, (d) cancer cells lacking GJIC either because of the non-expression of connexin genes or of non-functional gap junction proteins, and (e) the role of the microbiome in promoting initiated colon stem cells to divide symmetrically or asymmetrically are examined to find an explanation. It has been speculated that “embryonic-like” lesions in the ascending colon are initiated stem cells, promoted via symmetrical cell division, while the polyp-type lesions in the descending colon are initiated stem cells stimulated to divide asymmetrically. To test this hypothesis, experiments could be designed to examine if right-sided lesions might express Oct4A and ABCG2 genes but not any connexin genes, whereas the left-sided lesions might express a connexin gene, but not Oct4A or the ABCG2 genes. Treatment of the right sided lesions might include transcriptional regulators, whereas the left-sided lesions would need to restore the posttranslational status of the connexin proteins.

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References

  • Aasen T, Mesnil M, Naus CC, Lampe PD, Laird DW (2016) Gap junctions and cancer: communicating for 50 years. Nat Rev Cancer 16:775–788

    Article  CAS  PubMed  Google Scholar 

  • Ahuja D, Sáenz-Robles MT, Pipas JM (2005) SV40 large T antigen targets multiple cellular pathways to elicit cellular transformation. Oncogene 24:7729–7745. doi:10.1038/sj.onc.1209046

    Article  CAS  PubMed  Google Scholar 

  • 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 100:3983–3988

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Armstrong L, Tilgner K, Saretzki G, Atkinson SP, Stojkovic M, Moreno R, Przyborski S, Lako M (2010) Human induced pluripotent stem cell lines show stress defense mechanisms and mitochondrial regulation similar to those of human embryonic stem cells. Stem Cells 28:661–673

    Article  CAS  PubMed  Google Scholar 

  • Atena M, Reza AM, Meehran G (2014) A review on the biology of cancer stem cells. Stem Cell Discov 4:83–89. doi:10.4236/scd.2014.44009

    Article  CAS  Google Scholar 

  • Barker N (2014) Adult intestinal stem cells: critical drivers of epithelial homeostasis and regeneration. Nat Rev/Mol Cell Biol 15:19–33.02

    Article  CAS  Google Scholar 

  • Barker N, van Es JH, Kuipers J, Kujala P, van den Born M, Cozijnsen M, Haegebarth A, Korving J, Begthel H, Peters PJ, Clevers H (2007) Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 449:1003–1007

    Article  CAS  PubMed  Google Scholar 

  • Barker N, Ridgway RA, van Es JH, van de Wetering M, Begthel H, van den Born M, Danenberg E, Clarke AR, Sansom OJ, Clevers H (2009) Crypt stem cells as the cells-of-origin of intestinal cancer. Nature 457:608–611. doi:10.1038/nature076

    Article  CAS  PubMed  Google Scholar 

  • Berenblum PM (1954) A speculative review: the probable nature of promoting action and its significance in the understanding of the mechanisms of carcinogenesis. Cancer Res 14:471–477

    CAS  PubMed  Google Scholar 

  • Bongso A, Fong CY, Ng SC, Ratnam S (1994) Isolation and culture of inner cell mass cells from human blastocyts. Hum Reprod 9:2110–2117

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Brash DE, Rudolph JA, Simon JA, Lin A, McKenna GJ, Baden HP, Halperin AJ, Pontén J (1991) A role for sunlight in skin cancer: UV-induced p53 mutations in squamous cell carcinomas. Proc Natl Acad Sci U S A 88(22):10124–11018

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Brigelius-Flohé R, Flohé L (2011) Basic principles and emerging concepts in the redox control of transcription factors. Antioxid Redox Signal 15:2335–2381

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Brosnan CF, Scemes E, Spray DC (2001) Cytokine regulation of gap junction connectivity: an open-and-shut case or changing partners at the Nnxus? Am J Pathol 158(5):1565–1569

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bufill JA (1990) Colorectal cancer: evidence for distinct genetic categories based on proximal or distal tumor location. Ann Intern Med 113(10):779–788

    Article  CAS  PubMed  Google Scholar 

  • Chang CC, Trosko JE, El-Fouly MH, Gibson-D’Ambrosio R, D’Ambrosio SM (1987) Contact insensitivity of a subpopulation of normal human fetal kidney epithelial cells and of human carcinoma cell lines. Cancer Res 47:1634–1645

    CAS  PubMed  Google Scholar 

  • Chen CT, Shih YR, Kuo TK, Lee OK, Wei YH (2008) Coordinated changes of mitochondrial biogenesis and antioxidant enzymes during osteogenic differentiation of human mesenchymal stem cells. Stem Cells 26:960–968

    Article  CAS  PubMed  Google Scholar 

  • Cleaver JE (1978) Xeroderma pigmentosum: genetic and environmental influences in –skin carcinogenesis. J Dermatol 17(6):435–444

    CAS  Google Scholar 

  • Cleaver JE, Trosko JE (1970) Absence of excision of ultraviolet-induced cyclobutane dimers in xeroderma pigmentosum. Photochem Photobiol 11(6):547–550

    Article  CAS  PubMed  Google Scholar 

  • Cozzio A, Passegue E, Ayton PM, Karsunky H, Cleary ML, Weissman IL (2003) Similar MLL associated leukemias arising from self-renewing stem cells and short-lived myeloid progenitors. Genes Dev 17:3029–3035

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Crosnier C, Stamataki D, Lewis J (2006) Organizing cell renewal in the intestine: stem cell, signal and combinatorial control. Nat Rev/Genet 7:349–359

    Article  CAS  Google Scholar 

  • Cruciani V, Mikalsen SO (2006) The vertebrate connexin family. Cell Mol Life Sci 63:1125–1140

    Article  CAS  PubMed  Google Scholar 

  • Csete M (2005) Oxygen in the cultivation of stem cells. Ann N Y Acad Sci 1049:1–8

    Article  CAS  PubMed  Google Scholar 

  • de Jong J, Stoop H, Dohle GR, Bangma CH, Kliffen M, van Esser JW, van den Bent M, Kros JM, Oosterhuis JW, Looijenga LH (2005) Diagnostic value of OCT3/4 for pre-invasive an invasive testicular germ cell tumours. J Pathol 206:242–249

    Article  PubMed  Google Scholar 

  • DiPaolo JA (1983) Relative difficulties in transforming human and animal cells in vitro. J Natl Cancer Inst 70(1):3–8

    CAS  PubMed  Google Scholar 

  • Dougal K, Harris PA, Edwards A, Pachebat JA, Blackmore TM, Worgan HJ, Newbold CJ (2012) A comparison of the microbiome and the metabolome4 of different regions of the equine hindgut. FEMS Microbiol Ecol 82:642–652

    Article  CAS  PubMed  Google Scholar 

  • Eagle H (1965) Growth inhibitor effects of cellular interactions. Isr J Med Sci 1:1220–1228

    CAS  Google Scholar 

  • Fialkow PJ (1976) Clonal origin of human tumors. Annu Rev Med 30:135–176

    Article  Google Scholar 

  • Flemer B, Lynch DB, Brown JM, Jeffery IB, Ryan FJ, Claesson MJ, O'Riordain M, Shanahan F, O'Toole PW (2016). Tumour-associated and non-tumour associated microbiota in colorectal cancer. Gut. pii: gutjnl-2015-309595. doi: 10.1136/gutjnl-2015-309595.

  • Gagniere J, Raisch J, Veziant J, Barnich N, Bonnet R, Buc E et al (2016) Gut microbiota imbalance and colorectal cancer. World J Gastroenterol 22(2):501–518

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Galli R, Binda E, Orfanelli U, Cipelletti B, Gritti A, De Vitis S, Fiocco R, Foroni C, Dimeco F, Vescovi A (2004) Isolation and characterization of tumorigenic, stem-cell neural precursors from human glioblastoma. Cancer Res 64:7011–7021

    Article  CAS  PubMed  Google Scholar 

  • Gervaz P, Bucher P, Morel P (2004) Two colons-two cancers: paradigm shift and clinical implications. J Surg Oncol 88(4):261–266

    Article  PubMed  Google Scholar 

  • Glover TW, Chang CC, Trosko JE, Li SSL (1979) Ultraviolet light induction of diphtheria toxin resistant mutations in normal and xeroderma pigmentosum human fibroblasts. Proc Natl Acad Sci 76(3982):3986

    Google Scholar 

  • Gu G, Yuan J, Wills M, Kasper S (2007) Prostate cancer cells with stem cell characteristics reconstitute the original human tumor in vivo. Cancer Res 67:4807–4815

    Article  CAS  PubMed  Google Scholar 

  • Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70

    Article  CAS  PubMed  Google Scholar 

  • Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674

    Article  CAS  PubMed  Google Scholar 

  • Hayflick L (1965) The limited in vitro lifespan of human diploid cell strains. Exp Cell Res 37:614–636.815

    Article  CAS  PubMed  Google Scholar 

  • Heinemann V, Modest DP, von Weikensthal LF, Decker T, Kiani A, Veiling-Kaiser U, et al (2014). Gender and tumor location as predictors for efficacy: Influence on endpoints in firstline treatment with FOLFIRI in combination with cetuximab or bevacizumab in the AIO KRK 0306 (FIRE3) trial. J Clin Oncol 32(suppl; abstr 3600)

  • Hemmati HD, Nakano I, Lazareff JA, Masterman-Smith M, Geschwind DH, Bronner-Fraser M, Kornblum HI (2003) Cancerous stem cells can arise from pediatric brain tumors. Proc Natl Acad Sci U S A 100:15178–15183

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hill MA (2016) Embryology gastrointestinal tract development

  • Hope KJ, Jin L, Dick JE (2003) Human acute myeloid leukemia stem cells. Arch Med Res 34:507–514

    Article  CAS  PubMed  Google Scholar 

  • Horn T, Hilbrant M, Panfilio KA (2015) Evolution of epithelial morphogenesis: phenotypic integration across multiple levels of biological organization. Front Genet. doi:10.3389/fgene.2015.00303

    PubMed Central  PubMed  Google Scholar 

  • Houts AC OS, Sommer N, Walker MS (2016) Treatment patterns and outcomes in patients with KRAS wild type (WT) metastatic colorectal cancer (mCRC) treated in first line with bevacizumab (B) or cetuximab (C) containing regimens. J Clin Oncol 34

  • Huels DJ, Sansom OJ (2015) Stem versus non-stem cell origin of colorectal cancers. Brit J Cancer 113(1):1–5. doi:10.1038/bjc.2015.214

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Iacopetta B (2002) Are there two sides to colorectal cancer? Int J Cancer 101(5):403–408

    Article  CAS  PubMed  Google Scholar 

  • Jiang JX, Penuela S (2016) Connexin and pannexin channels in cancer. BMC Cell Biol 17(Suppl 1):512. doi:10.1186/s12860-016-0094-8

  • Kang S, Trosko JE (2011) Stem cells in toxicology: fundamental biology and practical considerations. Toxicol Sci 120(Suppl 1):S269–S289

    Article  CAS  PubMed  Google Scholar 

  • Kao CY, Nomata K, Oakley CS, Welsch CW, Chang CC (1995) Two types of normal human breast epithelial cells derived from reduction mammoplasty: phenotypic characterization and response to SV40 transfection. Carcinogenesis 16:531–538

    Article  CAS  PubMed  Google Scholar 

  • Kemper K, Prasetyanti PR, De Lau W, Rodermond H, Clevers H, Medema JP (2012) Monoclonal antibodies against Lgr5 identify human colorectal cancer stem cells. Stem Cells 30:2378–2386

    Article  CAS  PubMed  Google Scholar 

  • Klaunig J, Ruch RJ (1987) Strain and species effects on the inhibition of hepatocyte intercellular communication by liver tumor promoters. Cancer Lett 36:161–168

    Article  CAS  PubMed  Google Scholar 

  • Kondo T, Setoguchi T, Taga T (2004) Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line. Proc Natl Acad Sci U S A 101:781–786

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • 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 442:818–822

    Article  CAS  PubMed  Google Scholar 

  • Kuroki T, Huh N-H (1993) Why are human cells resistant to malignant cell transformation in vitro? Jpn J Cancer Res 84:1091–1100

    Article  CAS  PubMed  Google Scholar 

  • Land H, Parada LF, Weinberg RA (1983) Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature 304:596–602

    Article  CAS  PubMed  Google Scholar 

  • Lane SW, Williams DA, Watt FM (2014) Modulating the stem cell niche for tissue regeneration. Nat Biotechnol 32:795–803

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lee GH (2000) Paradoxical effects of phenobarbital on mouse hepatocarcinogenesis. Toxicol Pathol 28:215–225

    Article  CAS  PubMed  Google Scholar 

  • Leithe E, Sirnes S, Omori Y, Rivedal E (2006) Downregulation of gap junctions in +cancer cells. Crit Rev Oncog 12(3–4):225–256

    Article  PubMed  Google Scholar 

  • Lenz H, Lee F, Yau L, Koh H, Knost K, Mitchell E, et al. (2016). MAVERICC, a phase 2 study of mFOLFOX6bevacizumab (BV) vs FOLFIRIBV with biomarker stratification as firstline (1 L) chemotherapy (CT) in patients (pts) with metastatic colorectal cancer (mCRC). J Clin Oncol; 34(suppl 4S; abstr 493)

  • Leone A, Longo C, Trosko JE (2012) The chemopreventive role of dietary phytochemicals through gap junctional intercellular communication. Phytochem Rev. doi:10.1007/s11101-012-9235-7

    Google Scholar 

  • Li S, Yurchenco PD (2006) Matrix assembly, cell polarization, and cell survival: analysis of peri-implantation development with cultured embryonic stem cells. Methods Mol Biol 32:113–125

    Google Scholar 

  • Locke M, Heywood M, Fawell S, Mackenzie IC (2005) Retention of intrinsic stem cell hierarchies in carcinoma-derived cell lines. Cancer Res 65:8944–8950

    Article  CAS  PubMed  Google Scholar 

  • Loewenstein WR, Kanno Y (1966) Intercellular communication and the control of tissue growth: lack of communication between cancer cells. Nature 209:1248–1249

    Article  CAS  PubMed  Google Scholar 

  • Loupakis F, Yang D, Yau L, Feng S, Cremolini C, Zhang W, Maus MK, Antoniotti C, Langer C, Scherer SJ, Müller T, Hurwitz HI, Saltz L, Falcone A, Lenz HJ (2015a) Primary tumor location as a prognostic factor in metastatic colorectal cancer. J Natl Cancer Inst 107(3). doi:10.1093/jnci/dju427

  • Loupakis F, Yang D, Yau L, Feng S, Cremolini C, Zhang W et al (2015b) Primary tumor location as a prognostic factor in metastatic colorectal cancer. J Natl Cancer Inst 107(3)

  • Maher VM, McCormick JJ (1976) Effect of DNA repair on the cytotoxicity and mutagenicity of UV irradiation and of chemical carcinogens in normal and xeroderma pigmentosum cells. In: Yuhas JM, Tennant RW, Regan JD (eds) Biology of radiation carcinogenesis. Raven Press, New York, pp 129–145

    Google Scholar 

  • Markert CL (1968) Neoplasia: a disease of cell differentiation. Cancer Res 28:1908–1914

    CAS  PubMed  Google Scholar 

  • Martin FJ, Prince AS (1982) TLR2 regulates gap junction intercellular communication in airway cells. J Imm Biol Reprod 27(4):967–975

    Article  Google Scholar 

  • Mentink R, Tsiantis M (2015) From limbs to leaves: common themes in evolutionary diversification of organ form. Front Genet 6:284. doi:10.3389/fgene.2015.00284

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Missiaglia E, Jacobs B, D'Ario G, Di Narzo AF, Soneson C, Budinska E, Popovici V, Vecchione L, Gerster S, Yan P, Roth AD, Klingbiel D, Bosman FT, Delorenzi M, Tejpar S (2014) Distal and proximal colon cancers differ in terms of molecular, pathological, and clinical features. Ann Oncol 25:1995–2001. doi:10.1093/annonc/mdu275

    Article  CAS  PubMed  Google Scholar 

  • Mohyeldin A, Garzón-Muvdi T, Quiñones-Hinojosa A (2010) Oxygen in stem cell biology: a critical component of the stem cell niche. Cell Stem Cell 7(150):161

    Google Scholar 

  • Nava GM, Carbonero F, Croix JA, Greenberg E, Gaskins HR (2012) Abundance and diversity of muscosa-associated hydrogenotropic microbes in the healthy human colon. The ISME J 6:57–70

    Article  CAS  PubMed  Google Scholar 

  • Neste C, Pasquali L, Vaglini F, Siciliano G, Murri L (2007) The role of mitochondria in stem cell biology. Biosci Rep 27:165–171

    Article  CAS  Google Scholar 

  • Nitsche U, Stogbauer F, Spath C, Haller B, Wilhelm D, Friess H et al (2016) Right sided colon cancer as a distinct Histopathological subtype with reduced prognosis. Dig Surg 33(2):157–163

    Article  PubMed  Google Scholar 

  • O’Brien CA, Pollett A, Gallinger S, Dick JE (2007) A human colon cancer cell capable of initiating tumour growth in immune-deficient mice. Nature 445:106–110

    Article  CAS  PubMed  Google Scholar 

  • Ogawa T, Hayashi T, Tokunou M, Nakachi K, Trosko JE, Chang CC, Yorioka N (2005) Suberoylanilide hydroxamic acid enhances gap junctional intercellular communication on via acetylation of histone containing connexin43 gene locus. Cancer Res 65:9771–9778

    Article  CAS  PubMed  Google Scholar 

  • Pervaiz S, Taneja R, Ghaffari S (2009) Oxidative stress regulation of stem and progenitor cells. Antioxid Redox Signal 11:2777–2789

    Article  CAS  PubMed  Google Scholar 

  • Pierce GB (1974) Neoplasms, differentiation and mutations. Am J Pathol 77:103–118

    CAS  PubMed Central  PubMed  Google Scholar 

  • Pitot HC, Dragon Y (1991) Facts and theories concerning the mechanism of carcinogenesis. FASEB J 5:2280–2286

    CAS  PubMed  Google Scholar 

  • Ponti D, Costa A, Zaffaroni N, Pratesi G, Petrangolini G, Coradini D, Pilotti S, Pierotti MA, Daidone MG (2005) Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Res 65:5506–5511

    Article  CAS  PubMed  Google Scholar 

  • Potten CS, Gandara R, Mahida YR, Loeffler M, Wright NA (2009) The stem cells of small intestinal crypts: where are they? Cell Prolif 42:731–750

    Article  CAS  PubMed  Google Scholar 

  • Potter VR (1978) Phenotypic diversity in experimental hepatomas: the concept of partially blocked ontogeny. Br J Cancer 38:1–23

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Price TJ, Beeke C, Ullah S, Padbury R, Maddern G, Roder D et al (2015) Does the primary site of colorectal cancer impact outcomes for patients with metastatic disease? Cancer 9121(6):830–835

    Article  Google Scholar 

  • Prigione A, Fauler B, Lurz R, Lehrach H, Adjaye J (2010) The senescence related mitochondrial/oxidative stress pathway is repressed in human induced pluripotent stem cells. Stem Cells 28:721–733

    Article  CAS  PubMed  Google Scholar 

  • Puri CP, Garfield RE (1982) Changes in hormone levels and gap junctions in the rat uterus during pregnancy and parturition. Biol Reprod 27(4):967–7180

    Article  CAS  PubMed  Google Scholar 

  • Rhim JS (1993) Neoplastic transformation of human cells in vitro. Crit Rev Oncog 4:312–335

    Google Scholar 

  • Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, De Maria R (2007) Identification and expansion of human colon-cancer-initiating cells. Nature 445:111–115

    Article  CAS  PubMed  Google Scholar 

  • Ruch RJ, Trosko JE, Madhukar BV (2001) Inhibition of connexin43 gap junctional intercellular communication by TPA requires ERK activation. J Cell Biochem 83:163–169

    Article  CAS  PubMed  Google Scholar 

  • Sadler TW (2014) Langman's medical embryology. Wolters Kluwer, 12th edition, Philadelphia

  • Saez JC (2016) Proceedings of the international gap. BMC Cell Biol 17(Suppl 1):18. doi:10.1186/s12860-016-0097-5

    Article  PubMed Central  PubMed  Google Scholar 

  • Sanchez A, Hannezo E, Larsimont J-C, Liagre M, Youssef KK, Simons BD, Blanpain C (2016) Defining the clonal dynamics leading to mouse skin tumor initiation. Nature 536:298–303

    Article  CAS  Google Scholar 

  • Sato T, Clevers H (2013) Growing self-organizing mini-guts from a single intestinal stem cell: mechanism and applications. Science 340:1190–1194

    Article  CAS  PubMed  Google Scholar 

  • Schatton T, Murphy GF, Frank NY, Yamaura K, Waaga-Gasser AM, Gasser M, Zhan Q, Jordan S, Duncan LM, Weishaupt C, Fuhlbrigge RC, Kupper TS, Sayegh MH, Frank MH (2008) Identification of cells initiating human melanomas. Nature 451:345–349

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sell S (1993) Cellular origin of cancer: differentiation of stem cell maturation arrest? Environ Health Perspect 101:15–26

    Article  PubMed Central  PubMed  Google Scholar 

  • Shamblott MJ, Axelman J, Wang S, Bugg EM, Littlefield JW, Donovan PJ, Blumenthal PD, Huggins GR, Gearhart JD (1998) Derivation of pluripotent stem cells from cultured human primordial germ cells. PNAS, USA 95:13726–13731

    Article  CAS  Google Scholar 

  • Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, Dirks PB (2003) Identification of a cancer stem cell in human brain tumors. Cancer Res 63:5821–5828

    CAS  PubMed  Google Scholar 

  • Sinicrope FA, Mahoney MR, Yoon HH, Smyrk TC, Thibodeau SN, Goldberg RM et al (2015) Analysis of molecular markers by anatomic tumor site in stage III colon carcinomas from adjuvant chemotherapy trial NCCTG N0147 (alliance). Clin Cancer Res 21(23):5294–5304

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Tai M-H, Chang CC, Kiupel M, Webster JD, Olson LK, Trosko JE (2005) Oct-4 expression in adult stem cells: evidence in support of the stem cell theory of carcinogenesis. Carcinogenesis 26:495–502

    Article  CAS  PubMed  Google Scholar 

  • Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676

    Article  CAS  PubMed  Google Scholar 

  • Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM (1998) Embryonic stem cell lines derived from human blastocyts. Science 282:1145–1147

    Article  CAS  PubMed  Google Scholar 

  • Till JE (1982) Stem cells in differentiation and neoplasia. J Cell Physiol Suppl 1:3–11

    Article  CAS  PubMed  Google Scholar 

  • Trosko JE (2001) Is the concept of ‘tumor promotion’ a useful paradigm? Mol Carcinog 30:131–137

    Article  CAS  PubMed  Google Scholar 

  • Trosko JE (2003) The role of stem cells and gap junctional intercellular communication in carcinogenesis. J Biochem Mol Biol 36:43–48

    CAS  PubMed  Google Scholar 

  • Trosko JE (2006) From adult stem cells to cancer stem cells: Oct-4 gene, cell-cell communication, and hormones during tumor promotion. Ann NY Acad Sci 1089:36–58

    Article  CAS  PubMed  Google Scholar 

  • Trosko JE (2007) Gap junction intercellular communication as a ‘biological Rosetta stone’ in understanding, in a systems manner, stem cell behavior, mechanisms of epigenetic toxicology, chemoprevention and chemotherapy. J Membr Biol 218:93–100

    Article  CAS  PubMed  Google Scholar 

  • Trosko JEA (2008a) Commentary: re-programming or selecting adult stem cells. Stem Cell Rev 4:81–88

    Article  PubMed  Google Scholar 

  • Trosko J (2008b) Human adult stem cells as the target cells for the initiation of carcinogenesis and for the generation of “cancer stem cells”. Inter J Stem Cells 1:8–26

    Article  CAS  Google Scholar 

  • Trosko JE (2009) Cancer stem cells and cancer non-stem cells: from adult stem cells or from re-programming of differentiated somatic cells. Vet Pathol 46:176–193

    Article  CAS  PubMed  Google Scholar 

  • Trosko JE (2014) Induction of iPS cells and of cancer stem cells: the stem cell or reprogramming hypothesis of cancer? Anat Rec (Hoboken) 297:161–173

    Article  CAS  Google Scholar 

  • Trosko JE (2016a). A Conceptual integration of extra-, intra- and gap junctional-intercellular communication in the evolution of multi-cellularity and stem cells: how disrupted cell-cell communication during development can affect diseases later in life. Int J Stem Cell Res Ther 2016, 3:021, ISSN: 2469-570X

  • Trosko JE (2016b) Evolution of microbial quorum sensing to human global quorum sensing: an insight to how gap junctional intercellular communication might be linked to the global metabolic disease crisis. Biology (Basel).15;5(2). doi: 10.3390/biology5020029

  • Trosko JE, Chang CC (1988) Nongenotoxic mechanisms in carcinogenesis: role of inhibited intercellular communication. In: Hart RW and Hoerger FD (eds.) Banbury Report 31: carcinogen risk assessment: new directions in the qualitative and quantitative aspects. Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory. Pp.139–170

  • Trosko JE, Kang KS (2012) Evolution of energy metabolism, stem cells and cancer stem cells: how the Warburg and barker hypotheses might be linked. Int J Stem Cells 5:39–56

    Article  PubMed Central  PubMed  Google Scholar 

  • Trosko JE, Ruch RJ (1998) Cell-cell communication in carcinogenesis. Front Biosci 3:208–236

    Article  Google Scholar 

  • Trosko JE, Ruch R (2002) Gap junctions as targets for cancer chemoprevention and chemotherapy. Curr Drug Targets 203:465–482

    Article  Google Scholar 

  • Trosko JE, Tai MH (2006) Adult stem cell theory of the multi-stage, multi-mechanism theory of carcinogenesis: role of inflammation on the promotion of initiated cells. In Infections and Inflammation: Impacts on Oncogenesis; Dittmar, T., Zaenker, K.S., Schmidt, A., eds. Karger Publishers, Contributions to Microbiology: Basel, Switzerland, pp.45–65

  • Trosko JE, Chang CC, Madhukar BV, Oh SY (1990) Modulators of gap junction function: the scientific basis of epigenetic toxicology. In Vitro Toxicology 3:9–26

    CAS  Google Scholar 

  • Trosko JE, Chang CC, Upham BL, Wilson MR (1998) Epigenetic toxicology as toxicant-induced changes in intracellular signaling leading to altered gap junctional intercellular communication. Toxicol Lett 102-103:71–78

    Article  CAS  PubMed  Google Scholar 

  • Upham BL, Trosko JE (2009) Carcinogenic tumor promotion, induced oxidative stress signaling, modulated gap junction function and altered gene expression. Antioxid Redox 11:297–308

    Article  CAS  Google Scholar 

  • Venook A, Niedzwiecki D, Innocenti F, Fruth B, Greene C, O'Neil B et al. (2016) Impact of primary (1°) tumor location on overall survival (OS) and progressionfree survival (PFS) in patients (pts) with metastatic colorectal cancer (mCRC): Analysis of CALGB/SWOG 80405 (Alliance). J Clin Oncol 36(suppl; abstr 3504)

  • Wang X, Kruithof-de Julio M, Economides KD, Walker D, Yu H, Halili MV, Hu YP, Price SM, Abate-Shen C, Shen MM (2009) A luminal epithelial stem cell that is a cell of origin for prostate cancer. Nature 461:495–500

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Warburg O (1956) On respiratory impairment in cancer cells. Science 124:269–270

    CAS  PubMed  Google Scholar 

  • Warren S, Schultz RA, Chang CC, Wade MH, Trosko JE (1981) Elevated spontaneous mutation rate in bloom syndrome fibroblasts. Proc Natl Acad Sci USA 78:3133–3137

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Weinstein IB, Gattoni CS, Kirschmeier P, Lambert M, Hsiao W, Backer J, Jeffrey A (1984) Multistage carcinogenesis involves multiple genes and multiple mechanisms. J Cell Physiol 3:127–137

    Article  CAS  Google Scholar 

  • Weissman IL (2015) Stem cells are units of natural selection for tissue formation, for germline development and in cancer development. Proc Natl Acad Sci USA 112:8922–8928

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wilson MR, Close TW, Trosko JE (2000) Cell population dynamics (apoptosis, mitosis and cell-cell communication) during disruption of homeostasis. Exp Cell Res 254:257–268

    Article  CAS  PubMed  Google Scholar 

  • Wong HL, Lee B, Field K, Lomax A, Tacey M, Shapiro J et al (2016) Impact of primary tumor site on bevacizumab efficacy in metastatic colorectal cancer. Clin Colorectal Cancer 15(2):e9–e15

    Article  PubMed  Google Scholar 

  • Wu C, Wei Q, Utomo V, Nadesan P, Whetstone H, Kandel R, Wunder JS, Alman BA (2007) Side population cells isolated from mesenchymal neoplasms have tumor initiating potential. Cancer Res 67:8216–8222

    Article  CAS  PubMed  Google Scholar 

  • Yamagiwa K, Ichikawa K (1977) Experimental study of the pathogenesis of carcinoma. CA Cancer J Clin 27:174–181

    Article  CAS  PubMed  Google Scholar 

  • Yamasaki H, Naus CCG (1996) Role of connexin genes in growth control. Carcinogenesis 17:1199–1213

    Article  CAS  PubMed  Google Scholar 

  • Yamasaki H, Hollstein M, Mesnil M, Martel AAM (1987) Selectivel lack of intercellular communication between transformed and nontransformed cells as common property of chemical and oncogene transformation of BALB/c3T3 cells. Cancer Res 47:5658–5664

    CAS  PubMed  Google Scholar 

  • Yamauchi M, Morikawa T, Kuchiba A, Imamura Y, Qian ZR, Nishihara R et al (2012) Assessment of colorectal cancer molecular features along bowel subsites challenges the conception of distinct dichotomy of proximal versus distal colorectum. Gut 61(6):847–854

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Yotti LP, Trosko JE, Chang CC (1979) Elimination of metabolic cooperation in Chinese hamster cells by a tumor promoter. Science 206(1089):1091

    Google Scholar 

  • Yuan X, Curtin J, Xiong Y, Liu G, Waschsmann-Hogiu S, Farkas DL, Black KL, Yu JS (2004) Isolation of cancer stem cells from adult glioblastoma multiforme. Oncogene 23:9392–9400

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department Pediatrics and Human Development, College of Human Medicine, Michigan State University, 1129 Farm Lane, East Lansing, MI, 48824, USA

    James E. Trosko

  2. University of California Norris Comprehensive Cancer Center, Los Angeles, CA, USA

    Heinz-Josef Lenz

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  1. James E. Trosko
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  2. Heinz-Josef Lenz
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Correspondence to James E. Trosko.

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Trosko, J.E., Lenz, HJ. What roles do colon stem cells and gap junctions play in the left and right location of origin of colorectal cancers?. J. Cell Commun. Signal. 11, 79–87 (2017). https://doi.org/10.1007/s12079-017-0381-y

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  • DOI: https://doi.org/10.1007/s12079-017-0381-y

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