Wnt/beta-catenin signaling in embryonic stem cell converted tumor cells

详细信息    查看全文

• 作者：Xinrong Peng (1)
  Tao Liu (1)
  Ying Wang (1)
  Qiaoling Yan (1)
  Huajun Jin (1)
  Linfang Li (1)
  Qijun Qian (1) (2)
  Mengchao Wu (1)
  
• 关键词：Embryonic stem cell ; Malignancy ; Wnt/β ; catenin signaling
• 刊名：Journal of Translational Medicine
• 出版年：2012
• 出版时间：December 2012
• 年：2012
• 卷：10
• 期：1
• 全文大小：1754KB
• 参考文献：1. Martin GR: Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. / Proc Natl Acad Sci USA 1981, 78:7634-638. CrossRef
  2. Buehr M, Meek S, Blair K, Yang J, Ure J, Silva J, McLay R, Hall J, Ying QL, Smith A: Capture of authentic embryonic stem cells from rat blastocysts. / Cell 2008, 135:1287-298. CrossRef
  3. Evans MJ, Kaufman MH: Establishment in culture of pluripotential cells from mouse embryos. / Nature 1981, 292:154-56. CrossRef
  4. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM: Embryonic stem cell lines derived from human blastocysts. / Science 1998, 282:1145-147. CrossRef
  5. Hahn JW, Jagwani S, Kim E, Rendell VR, He J, Ezerskiy LA, Wesselschmidt R, Coscia CJ, Belcheva MM: Mu and kappa opioids modulate mouse embryonic stem cell-derived neural progenitor differentiation via MAP kinases. / J Neurochem 2010, 112:1431-441. CrossRef
  6. Raof NA, Mooney BM, Xie Y: Bioengineering embryonic stem cell microenvironments for the study of breast cancer. / Int J Mol Sci 2011, 12:7662-691. CrossRef
  7. Oktem G, Sanci M, Bilir A, Yildirim Y, Kececi SD, Ayla S, Inan S: Cancer stem cell and embryonic development-associated molecules contribute to prognostic significance in ovarian cancer. / Int J Gynecol Cancer 2012, 22:23-9. CrossRef
  8. Atlasi Y, Mowla SJ, Ziaee SA, Bahrami AR: OCT-4, an embryonic stem cell marker, is highly expressed in bladder cancer. / Int J Cancer 2007, 120:1598-602. CrossRef
  9. Kim J, Orkin SH: Embryonic stem cell-specific signatures in cancer: insights into genomic regulatory networks and implications for medicine. / Genome Med 2011, 3:75. CrossRef
  10. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S: Induction of pluripotent stem cells from adult human fibroblasts by defined factors. / Cell 2007, 131:861-72. CrossRef
  11. Takahashi K, Yamanaka S: Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. / Cell 2006, 126:663-76. CrossRef
  12. Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, / et al.: Induced pluripotent stem cell lines derived from human somatic cells. / Science 2007, 318:1917-920. CrossRef
  13. Kim JB, Sebastiano V, Wu G, Arauzo-Bravo MJ, Sasse P, Gentile L, Ko K, Ruau D, Ehrich M, van den Boom D, / et al.: Oct4-induced pluripotency in adult neural stem cells. / Cell 2009, 136:411-19. CrossRef
  14. Campbell KH, McWhir J, Ritchie WA, Wilmut I: Sheep cloned by nuclear transfer from a cultured cell line. / Nature 1996, 380:64-6. CrossRef
  15. Wells DN, Misica PM, Tervit HR, Vivanco WH: Adult somatic cell nuclear transfer is used to preserve the last surviving cow of the Enderby Island cattle breed. / Reprod Fertil Dev 1998, 10:369-78. CrossRef
  16. Ben-Porath I, Thomson MW, Carey VJ, Ge R, Bell GW, Regev A, Weinberg RA: An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. / Nat Genet 2008, 40:499-07. CrossRef
  17. Schoenhals M, Kassambara A, De Vos J, Hose D, Moreaux J, Klein B: Embryonic stem cell markers expression in cancers. / Biochem Biophys Res Commun 2009, 383:157-62. CrossRef
  18. Horst D, Kriegl L, Engel J, Jung A, Kirchner T: CD133 and nuclear beta-catenin: the marker combination to detect high risk cases of low stage colorectal cancer. / Eur J Cancer 2009, 45:2034-040. CrossRef
  19. Bafico A, Gazit A, Pramila T, Finch PW, Yaniv A, Aaronson SA: Interaction of frizzled related protein (FRP) with Wnt ligands and the frizzled receptor suggests alternative mechanisms for FRP inhibition of Wnt signaling. / J Biol Chem 1999, 274:16180-6187. CrossRef
  20. Sato N, Meijer L, Skaltsounis L, Greengard P, Brivanlou AH: Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor. / Nat Med 2004, 10:55-3. CrossRef
  21. Tanaka SS, Kojima Y, Yamaguchi YL, Nishinakamura R, Tam PP: Impact of WNT signaling on tissue lineage differentiation in the early mouse embryo. / Dev Growth Differ 2011, 53:843-56. CrossRef
  22. Takebe N, Harris PJ, Warren RQ, Ivy SP: Targeting cancer stem cells by inhibiting Wnt, notch, and hedgehog pathways. / Nat Rev Clin Oncol 2010, 8:97-06. CrossRef
  23. Espada J, Calvo MB, Diaz-Prado S, Medina V: Wnt signalling and cancer stem cells. / Clin Transl Oncol 2009, 11:411-27. CrossRef
  24. Vermeulen L, De Sousa EMF, van der Heijden M, Cameron K, de Jong JH, Borovski T, Tuynman JB, Todaro M, Merz C, Rodermond H, / et al.: Wnt activity defines colon cancer stem cells and is regulated by the microenvironment. / Nat Cell Biol 2010, 12:468-76. CrossRef
  25. Ying QL, Wray J, Nichols J, Batlle-Morera L, Doble B, Woodgett J, Cohen P, Smith A: The ground state of embryonic stem cell self-renewal. / Nature 2008, 453:519-23. CrossRef
  26. Yasumura Y, Buonassisi V, Sato G: Clonal analysis of differentiated function in animal cell cultures. I. Possible correlated maintenance of differentiated function and the diploid karyotype. / Cancer Res 1966, 26:529-35.
  27. Ying QL, Nichols J, Evans EP, Smith AG: Changing potency by spontaneous fusion. / Nature 2002, 416:545-48. CrossRef
  28. Tao Liu YW, Xinrong P, Liqing Z, Jingbo C, Huajun J, Mengchao W, Qijun Q: Establishment of mouse teratocarcinomas stem cells line and screening genes responsible for malignancy. / PLoS One 2012, 7:e43955. CrossRef
  29. Murray JT, Campbell DG, Morrice N, Auld GC, Shpiro N, Marquez R, Peggie M, Bain J, Bloomberg GB, Grahammer F, / et al.: Exploitation of KESTREL to identify NDRG family members as physiological substrates for SGK1 and GSK3. / Biochem J 2004, 384:477-88. CrossRef
  30. Shutes A, Onesto C, Picard V, Leblond B, Schweighoffer F, Der CJ: Specificity and mechanism of action of EHT 1864, a novel small molecule inhibitor of Rac family small GTPases. / J Biol Chem 2007, 282:35666-5678. CrossRef
  31. Postovit LM, Margaryan NV, Seftor EA, Kirschmann DA, Lipavsky A, Wheaton WW, Abbott DE, Seftor RE, Hendrix MJ: Human embryonic stem cell microenvironment suppresses the tumorigenic phenotype of aggressive cancer cells. / Proc Natl Acad Sci USA 2008, 105:4329-334. CrossRef
  32. Hendrix MJ, Seftor EA, Seftor RE, Kasemeier-Kulesa J, Kulesa PM, Postovit LM: Reprogramming metastatic tumour cells with embryonic microenvironments. / Nat Rev Cancer 2007, 7:246-55. CrossRef
  33. Topczewska JM, Postovit LM, Margaryan NV, Sam A, Hess AR, Wheaton WW, Nickoloff BJ, Topczewski J, Hendrix MJ: Embryonic and tumorigenic pathways converge via nodal signaling: role in melanoma aggressiveness. / Nat Med 2006, 12:925-32. CrossRef
  34. Balint K, Xiao M, Pinnix CC, Soma A, Veres I, Juhasz I, Brown EJ, Capobianco AJ, Herlyn M, Liu ZJ: Activation of Notch1 signaling is required for beta-catenin-mediated human primary melanoma progression. / J Clin Invest 2005, 115:3166-176. CrossRef
  35. Schneider M, Huber J, Hadaschik B, Siegers GM, Fiebig HH, Schuler J: Characterization of colon cancer cells: a functional approach characterizing CD133 as a potential stem cell marker. / BMC Cancer 2012, 12:96. CrossRef
  36. Wu Y, Wu PY: CD133 as a marker for cancer stem cells: progresses and concerns. / Stem Cells Dev 2009, 18:1127-134. CrossRef
  37. Colnot S, Decaens T, Niwa-Kawakita M, Godard C, Hamard G, Kahn A, Giovannini M, Perret C: Liver-targeted disruption of Apc in mice activates beta-catenin signaling and leads to hepatocellular carcinomas. / Proc Natl Acad Sci USA 2004, 101:17216-7221. CrossRef
  38. Thevenod F, Chakraborty PK: The role of Wnt/beta-catenin signaling in renal carcinogenesis: lessons from cadmium toxicity studies. / Curr Mol Med 2010, 10:387-04. CrossRef
  
• 作者单位：Xinrong Peng (1)
  Tao Liu (1)
  Ying Wang (1)
  Qiaoling Yan (1)
  Huajun Jin (1)
  Linfang Li (1)
  Qijun Qian (1) (2)
  Mengchao Wu (1)
  
  1. Laboratory of Viral and Gene Therapy, Eastern Hepatobiliary Surgical Hospital, The Second Military Medical University, Shanghai, China
  2. Xinyuan Institute of Medicine and Biotechnology, College of Life Science, Zhejiang Sci-Tech University, Hangzhou, Zhejiang, China
  

文摘

Background Embryonic stem cells (ESCs) are pluripotent stem cells and can form tumors containing cells from all three germ layers. Similarities between pluripotent stem cells and malignant tumor cells have been identified. The purpose of this study was to obtain ESCs-converted tumor cell lines and to investigate the mechanism of malignancy in pluripotent stem cells. Methods Mouse ESCs were subcutaneously injected into nude mice to obtain tumors from which a tumor-like cell line (ECCs1) was established by culturing the cells in chemical-defined N2B27 medium supplied with two small molecular inhibitors CHIR99021 and PD0325901 (2i). The ECCs1 were then subcutaneously injected into nude mice again to obtain tumors from which another tumor-like cells line (ECCs2) was established in the same 2i medium. The malignant degree of ESCs, ECCs1 and ECCs2 was compared and the underlying mechanism involved in the malignancy development of ESCs was examined. Results The three ESCs, ECCs1 and ECCs2 cell lines were cultured in the same 2i condition and showed some likeness such as Oct4-expression and long-term expansion ability. However, the morphology and the tumor-formation ability of the cell lines were different. We identified that ECCs1 and ECCs2 gradually acquired malignancy. Moreover, Wnt signaling-related genes such as CD133 and β-catenin expression were up-regulated and Frizzled related protein (FRP) was down-regulated during the tumor development of ESCs. Conclusions The two tumor-like cell lines ECCs1 and ECCs2 stand for early malignant development stage of ESCs and the ECCs2 was more malignant than the ECCs1. Moreover, we identified that Wnt/β-catenin signaling played an important role in the malignancy process of ESCs.