Dysregulation of signaling pathways and putative biomarkers in liver cancer stem cells (Review)
- Authors:
- Kai Song
- Junhua Wu
- Chunping Jiang
-
Affiliations: Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, P.R. China, School of Medicine, Nanjing University, Nanjing, Jiangsu, P.R. China - Published online on: October 17, 2012 https://doi.org/10.3892/or.2012.2082
- Pages: 3-12
This article is mentioned in:
Abstract
Yu MC and Yuan JM: Environmental factors and risk for hepatocellular carcinoma. Gastroenterology. 127(Suppl 1): S72–S78. 2004. View Article : Google Scholar : PubMed/NCBI | |
Bosch FX, Ribes J, Cleries R and Diaz M: Epidemiology of hepatocellular carcinoma. Clin Liver Dis. 9:191–211. 2005. View Article : Google Scholar : PubMed/NCBI | |
Gomaa AI, Khan SA, Toledano MB, Waked I and Taylor-Robinson SD: Hepatocellular carcinoma: epidemiology, risk factors and pathogenesis. World J Gastroenterol. 14:4300–4308. 2008. View Article : Google Scholar : PubMed/NCBI | |
Shariff MI, Cox IJ, Gomaa AI, Khan SA, Gedroyc W and Taylor-Robinson SD: Hepatocellular carcinoma: current trends in worldwide epidemiology, risk factors, diagnosis and therapeutics. Expert Rev Gastroenterol Hepatol. 3:353–367. 2009. View Article : Google Scholar : PubMed/NCBI | |
Kumar M, Kumar R, Hissar SS, et al: Risk factors analysis for hepatocellular carcinoma in patients with and without cirrhosis: a case-control study of 213 hepatocellular carcinoma patients from India. J Gastroenterol Hepatol. 22:1104–1111. 2007. View Article : Google Scholar : PubMed/NCBI | |
Carr BI: Hepatocellular carcinoma: current management and future trends. Gastroenterology. 127(Suppl 1): S218–S224. 2004. View Article : Google Scholar : PubMed/NCBI | |
Kassahun WT, Fangmann J, Harms J, Hauss J and Bartels M: Liver resection and transplantation in the management of hepatocellular carcinoma: a review. Exp Clin Transplant. 4:549–558. 2006.PubMed/NCBI | |
Witjes CD, Verhoef C, Verheul HM and Eskens FA: Systemic treatment in hepatocellular carcinoma; ‘A small step for man’. Neth J Med. 67:86–90. 2009. | |
Reya T, Morrison SJ, Clarke MF and Weissman IL: Stem cells, cancer, and cancer stem cells. Nature. 414:105–111. 2001. View Article : Google Scholar : PubMed/NCBI | |
Bonnet D and Dick JE: Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 3:730–737. 1997. View Article : Google Scholar : PubMed/NCBI | |
Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ and Clarke MF: Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA. 100:3983–3988. 2003. View Article : Google Scholar : PubMed/NCBI | |
Collins AT, Berry PA, Hyde C, Stower MJ and Maitland NJ: Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res. 65:10946–10951. 2005. View Article : Google Scholar : PubMed/NCBI | |
Klarmann GJ, Hurt EM, Mathews LA, et al: Invasive prostate cancer cells are tumor initiating cells that have a stem cell-like genomic signature. Clin Exp Metastasis. 26:433–446. 2009. View Article : Google Scholar : PubMed/NCBI | |
Kim CF, Jackson EL, Woolfenden AE, et al: Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell. 121:823–835. 2005. View Article : Google Scholar : PubMed/NCBI | |
Eramo A, Lotti F, Sette G, et al: Identification and expansion of the tumorigenic lung cancer stem cell population. Cell Death Differ. 15:504–514. 2008. View Article : Google Scholar : PubMed/NCBI | |
O’Brien CA, Pollett A, Gallinger S and Dick JE: A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature. 445:106–110. 2007.PubMed/NCBI | |
Chu P, Clanton DJ, Snipas TS, et al: Characterization of a subpopulation of colon cancer cells with stem cell-like properties. Int J Cancer. 124:1312–1321. 2009. View Article : Google Scholar : PubMed/NCBI | |
Li C, Heidt DG, Dalerba P, et al: Identification of pancreatic cancer stem cells. Cancer Res. 67:1030–1037. 2007. View Article : Google Scholar : PubMed/NCBI | |
Li C, Lee CJ and Simeone DM: Identification of human pancreatic cancer stem cells. Methods Mol Biol. 568:161–173. 2009. View Article : Google Scholar : PubMed/NCBI | |
Singh SK, Clarke ID, Terasaki M, et al: Identification of a cancer stem cell in human brain tumors. Cancer Res. 63:5821–5828. 2003.PubMed/NCBI | |
Rahman R, Heath R and Grundy R: Cellular immortality in brain tumours: an integration of the cancer stem cell paradigm. Biochim Biophys Acta. 1792:280–288. 2009. View Article : Google Scholar : PubMed/NCBI | |
Sun YL, Yin SY, Xie HY, et al: Stem-like cells in hepatitis B virus-associated cirrhotic livers and adjacent tissue to hepatocellular carcinomas possess the capacity of tumorigenicity. J Gastroenterol Hepatol. 23:1280–1286. 2008. View Article : Google Scholar : PubMed/NCBI | |
Roskams TA, Theise ND, Balabaud C, et al: Nomenclature of the finer branches of the biliary tree: canals, ductules, and ductular reactions in human livers. Hepatology. 39:1739–1745. 2004. View Article : Google Scholar : PubMed/NCBI | |
Petersen BE, Bowen WC, Patrene KD, et al: Bone marrow as a potential source of hepatic oval cells. Science. 284:1168–1170. 1999.PubMed/NCBI | |
Shi XL, Gu JY, Han B, Xu HY, Fang L and Ding YT: Magnetically labeled mesenchymal stem cells after autologous transplantation into acutely injured liver. World J Gastroenterol. 16:3674–3679. 2010. View Article : Google Scholar : PubMed/NCBI | |
Theise ND, Nimmakayalu M, Gardner R, et al: Liver from bone marrow in humans. Hepatology. 32:11–16. 2000. View Article : Google Scholar | |
Rowe PM: Chronic Lyme disease: the debate goes on. Lancet. 355:14362000. View Article : Google Scholar : PubMed/NCBI | |
Bae SH, Choi JY, Yoon SK, et al: Thy1-positive bone marrow stem cells express liver-specific genes in vitro and can mature into hepatocytes in vivo. Hepatol Int. 2:63–71. 2008. View Article : Google Scholar : PubMed/NCBI | |
Gournay J, Auvigne I, Pichard V, Ligeza C, Bralet MP and Ferry N: In vivo cell lineage analysis during chemical hepatocarcinogenesis in rats using retroviral-mediated gene transfer: evidence for dedifferentiation of mature hepatocytes. Lab Invest. 82:781–788. 2002. View Article : Google Scholar | |
Bralet MP, Pichard V and Ferry N: Demonstration of direct lineage between hepatocytes and hepatocellular carcinoma in diethylnitrosamine-treated rats. Hepatology. 36:623–630. 2002. View Article : Google Scholar : PubMed/NCBI | |
Dumble ML, Croager EJ, Yeoh GC and Quail EA: Generation and characterization of p53 null transformed hepatic progenitor cells: oval cells give rise to hepatocellular carcinoma. Carcinogenesis. 23:435–445. 2002. View Article : Google Scholar : PubMed/NCBI | |
Fujii T, Zen Y, Harada K, et al: Participation of liver cancer stem/progenitor cells in tumorigenesis of scirrhous hepatocellular carcinoma - human and cell culture study. Hum Pathol. 39:1185–1196. 2008. View Article : Google Scholar : PubMed/NCBI | |
Nomoto K, Tsuneyama K, Cheng C, et al: Intrahepatic cholangiocarcinoma arising in cirrhotic liver frequently expressed p63-positive basal/stem-cell phenotype. Pathol Res Pract. 202:71–76. 2006. View Article : Google Scholar | |
Tanaka S, Yamamoto T, Tanaka H, et al: Potentiality of combined hepatocellular and intrahepatic cholangiocellular carcinoma originating from a hepatic precursor cell: immunohistochemical evidence. Hepatol Res. 32:52–57. 2005. View Article : Google Scholar | |
Zhang F, Chen XP, Zhang W, et al: Combined hepatocellular cholangiocarcinoma originating from hepatic progenitor cells: immunohistochemical and double-fluorescence immunostaining evidence. Histopathology. 52:224–232. 2008. View Article : Google Scholar | |
Komuta M, Spee B, Vander Borght S, et al: Clinicopathological study on cholangiolocellular carcinoma suggesting hepatic progenitor cell origin. Hepatology. 47:1544–1556. 2008. View Article : Google Scholar : PubMed/NCBI | |
de Lima VM, Oliveira CP, Alves VA, et al: A rodent model of NASH with cirrhosis, oval cell proliferation and hepatocellular carcinoma. J Hepatol. 49:1055–1061. 2008.PubMed/NCBI | |
Grozdanov PN, Yovchev MI and Dabeva MD: The oncofetal protein glypican-3 is a novel marker of hepatic progenitor/oval cells. Lab Invest. 86:1272–1284. 2006. View Article : Google Scholar : PubMed/NCBI | |
Caja L, Ortiz C, Bertran E, et al: Differential intracellular signalling induced by TGF-beta in rat adult hepatocytes and hepatoma cells: implications in liver carcinogenesis. Cell Signal. 19:683–694. 2007. View Article : Google Scholar : PubMed/NCBI | |
Herzer K, Grosse-Wilde A, Krammer PH, Galle PR and Kanzler S: Transforming growth factor-beta-mediated tumor necrosis factor-related apoptosis-inducing ligand expression and apoptosis in hepatoma cells requires functional cooperation between Smad proteins and activator protein-1. Mol Cancer Res. 6:1169–1177. 2008. View Article : Google Scholar | |
Wang CL, Wan YL, Liu YC and Huang ZQ: TGF-beta1/SMAD signaling pathway mediates p53-dependent apoptosis in hepatoma cell lines. Chin Med Sci J. 21:33–35. 2006.PubMed/NCBI | |
Yang YA, Zhang GM, Feigenbaum L and Zhang YE: Smad3 reduces susceptibility to hepatocarcinoma by sensitizing hepatocytes to apoptosis through downregulation of Bcl-2. Cancer Cell. 9:445–457. 2006. View Article : Google Scholar : PubMed/NCBI | |
Kiyono K, Suzuki HI, Matsuyama H, et al: Autophagy is activated by TGF-beta and potentiates TGF-beta-mediated growth inhibition in human hepatocellular carcinoma cells. Cancer Res. 69:8844–8852. 2009. View Article : Google Scholar : PubMed/NCBI | |
Mazzocca A, Fransvea E, Lavezzari G, Antonaci S and Giannelli G: Inhibition of transforming growth factor beta receptor I kinase blocks hepatocellular carcinoma growth through neo-angiogenesis regulation. Hepatology. 50:1140–1151. 2009. View Article : Google Scholar | |
Mikula M, Proell V, Fischer AN and Mikulits W: Activated hepatic stellate cells induce tumor progression of neoplastic hepatocytes in a TGF-beta dependent fashion. J Cell Physiol. 209:560–567. 2006. View Article : Google Scholar : PubMed/NCBI | |
Bae HJ, Eun JW, Noh JH, et al: Down-regulation of transforming growth factor beta receptor type III in hepatocellular carcinoma is not directly associated with genetic alterations or loss of heterozygosity. Oncol Rep. 22:475–480. 2009.PubMed/NCBI | |
Ji GZ, Wang XH, Miao L, et al: Role of transforming growth factor-beta1-smad signal transduction pathway in patients with hepatocellular carcinoma. World J Gastroenterol. 12:644–648. 2006.PubMed/NCBI | |
Lin SJ, Chang C, Ng AK, Wang SH, Li JJ and Hu CP: Prevention of TGF-beta-induced apoptosis by interleukin-4 through Akt activation and p70S6K survival signaling pathways. Apoptosis. 12:1659–1670. 2007. View Article : Google Scholar : PubMed/NCBI | |
Millet C and Zhang YE: Roles of Smad3 in TGF-beta signaling during carcinogenesis. Crit Rev Eukaryot Gene Expr. 17:281–293. 2007. View Article : Google Scholar : PubMed/NCBI | |
Zhang S, Fei T, Zhang L, et al: Smad7 antagonizes transforming growth factor beta signaling in the nucleus by interfering with functional Smad-DNA complex formation. Mol Cell Biol. 27:4488–4499. 2007. View Article : Google Scholar : PubMed/NCBI | |
Kitisin K, Ganesan N, Tang Y, et al: Disruption of transforming growth factor-beta signaling through beta-spectrin ELF leads to hepatocellular cancer through cyclin D1 activation. Oncogene. 26:7103–7110. 2007. View Article : Google Scholar : PubMed/NCBI | |
Baek HJ, Lim SC, Kitisin K, et al: Hepatocellular cancer arises from loss of transforming growth factor beta signaling adaptor protein embryonic liver fodrin through abnormal angiogenesis. Hepatology. 48:1128–1137. 2008. View Article : Google Scholar | |
Carmona-Cuenca I, Roncero C, Sancho P, et al: Upregulation of the NADPH oxidase NOX4 by TGF-beta in hepatocytes is required for its pro-apoptotic activity. J Hepatol. 49:965–976. 2008. View Article : Google Scholar : PubMed/NCBI | |
Caja L, Sancho P, Bertran E, Iglesias-Serret D, Gil J and Fabregat I: Overactivation of the MEK/ERK pathway in liver tumor cells confers resistance to TGF-{beta}-induced cell death through impairing up-regulation of the NADPH oxidase NOX4. Cancer Res. 69:7595–7602. 2009.PubMed/NCBI | |
Sheahan S, Bellamy CO, Dunbar DR, Harrison DJ and Prost S: Deficiency of G1 regulators P53, P21Cip1 and/or pRb decreases hepatocyte sensitivity to TGFbeta cell cycle arrest. BMC Cancer. 7:2152007. View Article : Google Scholar : PubMed/NCBI | |
Zulehner G, Mikula M, Schneller D, et al: Nuclear beta-catenin induces an early liver progenitor phenotype in hepatocellular carcinoma and promotes tumor recurrence. Am J Pathol. 176:472–481. 2010. View Article : Google Scholar : PubMed/NCBI | |
Tang Y, Kitisin K, Jogunoori W, et al: Progenitor/stem cells give rise to liver cancer due to aberrant TGF-beta and IL-6 signaling. Proc Natl Acad Sci USA. 105:2445–2450. 2008. View Article : Google Scholar : PubMed/NCBI | |
Lin L, Amin R, Gallicano GI, et al: The STAT3 inhibitor NSC 74859 is effective in hepatocellular cancers with disrupted TGF-beta signaling. Oncogene. 28:961–972. 2009. View Article : Google Scholar : PubMed/NCBI | |
Bagnyukova TV, Tryndyak VP, Muskhelishvili L, Ross SA, Beland FA and Pogribny IP: Epigenetic downregulation of the suppressor of cytokine signaling 1 (Socs1) gene is associated with the STAT3 activation and development of hepatocellular carcinoma induced by methyl-deficiency in rats. Cell Cycle. 7:3202–3210. 2008. View Article : Google Scholar : PubMed/NCBI | |
Dajani R, Fraser E, Roe SM, et al: Structural basis for recruitment of glycogen synthase kinase 3beta to the axin-APC scaffold complex. EMBO J. 22:494–501. 2003. View Article : Google Scholar : PubMed/NCBI | |
Ha NC, Tonozuka T, Stamos JL, Choi HJ and Weis WI: Mechanism of phosphorylation-dependent binding of APC to beta-catenin and its role in beta-catenin degradation. Mol Cell. 15:511–521. 2004. View Article : Google Scholar : PubMed/NCBI | |
Tauriello DV, Jordens I, Kirchner K, et al: Wnt/β-catenin signaling requires interaction of the Dishevelled DEP domain and C terminus with a discontinuous motif in Frizzled. Proc Natl Acad Sci USA. 109:E812–E820. 2012. | |
Tetsu O and McCormick F: Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature. 398:422–426. 1999. View Article : Google Scholar : PubMed/NCBI | |
Yochum GS, Sherrick CM, Macpartlin M and Goodman RH: A beta-catenin/TCF-coordinated chromatin loop at MYC integrates 5′ and 3′ Wnt responsive enhancers. Proc Natl Acad Sci USA. 107:145–150. 2010.PubMed/NCBI | |
Staal FJ, Meeldijk J, Moerer P, et al: Wnt signaling is required for thymocyte development and activates Tcf-1 mediated transcription. Eur J Immunol. 31:285–293. 2001. View Article : Google Scholar : PubMed/NCBI | |
Taniguchi H and Chiba T: Stem cells and cancer in the liver. Dis Markers. 24:223–229. 2008. View Article : Google Scholar | |
Takigawa Y and Brown AM: Wnt signaling in liver cancer. Curr Drug Targets. 9:1013–1024. 2008. View Article : Google Scholar : PubMed/NCBI | |
Wang M, Xue L, Cao Q, et al: Expression of Notch1, Jagged1 and beta-catenin and their clinicopathological significance in hepatocellular carcinoma. Neoplasma. 56:533–541. 2009. View Article : Google Scholar : PubMed/NCBI | |
Wei W, Chua MS, Grepper S and So SK: Blockade of Wnt-1 signaling leads to anti-tumor effects in hepatocellular carcinoma cells. Mol Cancer. 8:762009. View Article : Google Scholar : PubMed/NCBI | |
Yuzugullu H, Benhaj K, Ozturk N, et al: Canonical Wnt signaling is antagonized by noncanonical Wnt5a in hepatocellular carcinoma cells. Mol Cancer. 8:902009. View Article : Google Scholar : PubMed/NCBI | |
Toyama T, Lee HC, Koga H, Wands JR and Kim M: Noncanonical Wnt11 inhibits hepatocellular carcinoma cell proliferation and migration. Mol Cancer Res. 8:254–265. 2010. View Article : Google Scholar : PubMed/NCBI | |
Yonemitsu Y, Imazeki F, Chiba T, et al: Distinct expression of polycomb group proteins EZH2 and BMI1 in hepatocellular carcinoma. Hum Pathol. 40:1304–1311. 2009. View Article : Google Scholar : PubMed/NCBI | |
Chiba T, Miyagi S, Saraya A, et al: The polycomb gene product BMI1 contributes to the maintenance of tumor-initiating side population cells in hepatocellular carcinoma. Cancer Res. 68:7742–7749. 2008. View Article : Google Scholar : PubMed/NCBI | |
Chiba T, Suzuki E, Negishi M, et al: 3-Deazaneplanocin A is a promising therapeutic agent for the eradication of tumor-initiating hepatocellular carcinoma cells. Int J Cancer. 130:2557–2567. 2012. View Article : Google Scholar : PubMed/NCBI | |
Cheng AS, Lau SS, Chen Y, et al: EZH2-mediated concordant repression of Wnt antagonists promotes β-catenin-dependent hepatocarcinogenesis. Cancer Res. 71:4028–4039. 2011.PubMed/NCBI | |
Zaret KS: Genetic programming of liver and pancreas progenitors: lessons for stem-cell differentiation. Nat Rev Genet. 9:329–340. 2008. View Article : Google Scholar : PubMed/NCBI | |
Yamashita T, Budhu A, Forgues M and Wang XW: Activation of hepatic stem cell marker EpCAM by Wnt-beta-catenin signaling in hepatocellular carcinoma. Cancer Res. 67:10831–10839. 2007. View Article : Google Scholar : PubMed/NCBI | |
Yamashita T, Ji J, Budhu A, et al: EpCAM-positive hepatocellular carcinoma cells are tumor-initiating cells with stem/progenitor cell features. Gastroenterology. 136:1012–1024. 2009. View Article : Google Scholar : PubMed/NCBI | |
Yin L, Velazquez OC and Liu ZJ: Notch signaling: emerging molecular targets for cancer therapy. Biochem Pharmacol. 80:690–701. 2010. View Article : Google Scholar : PubMed/NCBI | |
Sharma VM, Draheim KM and Kelliher MA: The Notch1/c-Myc pathway in T cell leukemia. Cell Cycle. 6:927–930. 2007. View Article : Google Scholar : PubMed/NCBI | |
Moserle L, Ghisi M, Amadori A and Indraccolo S: Side population and cancer stem cells: therapeutic implications. Cancer Lett. 288:1–9. 2010. View Article : Google Scholar : PubMed/NCBI | |
Wu WK, Cho CH, Lee CW, et al: Dysregulation of cellular signaling in gastric cancer. Cancer Lett. 295:144–153. 2010. View Article : Google Scholar : PubMed/NCBI | |
Moellering RE, Cornejo M, Davis TN, et al: Direct inhibition of the NOTCH transcription factor complex. Nature. 462:182–188. 2009. View Article : Google Scholar : PubMed/NCBI | |
Arora PS and Ansari AZ: Chemical biology: A Notch above other inhibitors. Nature. 462:171–173. 2009. View Article : Google Scholar : PubMed/NCBI | |
Farnie G and Clarke RB: Mammary stem cells and breast cancer - role of Notch signalling. Stem Cell Rev. 3:169–175. 2007. View Article : Google Scholar : PubMed/NCBI | |
Stylianou S, Clarke RB and Brennan K: Aberrant activation of notch signaling in human breast cancer. Cancer Res. 66:1517–1525. 2006. View Article : Google Scholar : PubMed/NCBI | |
Zardawi SJ, Zardawi I, McNeil CM, et al: High Notch1 protein expression is an early event in breast cancer development and is associated with the HER-2 molecular subtype. Histopathology. 56:286–296. 2010. View Article : Google Scholar : PubMed/NCBI | |
Mittal S, Subramanyam D, Dey D, Kumar RV and Rangarajan A: Cooperation of Notch and Ras/MAPK signaling pathways in human breast carcinogenesis. Mol Cancer. 8:1282009. View Article : Google Scholar : PubMed/NCBI | |
Hirose H, Ishii H, Mimori K, et al: Notch pathway as candidate therapeutic target in Her2/Neu/ErbB2 receptor-negative breast tumors. Oncol Rep. 23:35–43. 2010.PubMed/NCBI | |
Korkaya H and Wicha MS: HER-2, notch, and breast cancer stem cells: targeting an axis of evil. Clin Cancer Res. 15:1845–1847. 2009. View Article : Google Scholar : PubMed/NCBI | |
Wang C, Qi R, Li N, et al: Notch1 signaling sensitizes tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in human hepatocellular carcinoma cells by inhibiting Akt/Hdm2-mediated p53 degradation and up-regulating p53-dependent DR5 expression. J Biol Chem. 284:16183–16190. 2009. View Article : Google Scholar | |
Gramantieri L, Giovannini C, Lanzi A, et al: Aberrant Notch3 and Notch4 expression in human hepatocellular carcinoma. Liver Int. 27:997–1007. 2007. View Article : Google Scholar : PubMed/NCBI | |
Sikandar SS, Pate KT, Anderson S, et al: NOTCH signaling is required for formation and self-renewal of tumor-initiating cells and for repression of secretory cell differentiation in colon cancer. Cancer Res. 70:1469–1478. 2010. View Article : Google Scholar : PubMed/NCBI | |
Harrison H, Farnie G, Howell SJ, et al: Regulation of breast cancer stem cell activity by signaling through the Notch4 receptor. Cancer Res. 70:709–718. 2010. View Article : Google Scholar : PubMed/NCBI | |
Zhen Y, Zhao S, Li Q, Li Y and Kawamoto K: Arsenic trioxide-mediated Notch pathway inhibition depletes the cancer stem-like cell population in gliomas. Cancer Lett. 292:64–72. 2010. View Article : Google Scholar : PubMed/NCBI | |
Hambardzumyan D, Becher OJ and Holland EC: Cancer stem cells and survival pathways. Cell Cycle. 7:1371–1378. 2008. View Article : Google Scholar | |
Huang S, He J, Zhang X, et al: Activation of the hedgehog pathway in human hepatocellular carcinomas. Carcinogenesis. 27:1334–1340. 2006. View Article : Google Scholar : PubMed/NCBI | |
Cheng WT, Xu K, Tian DY, Zhang ZG, Liu LJ and Chen Y: Role of Hedgehog signaling pathway in proliferation and invasiveness of hepatocellular carcinoma cells. Int J Oncol. 34:829–836. 2009.PubMed/NCBI | |
Patil MA, Zhang J, Ho C, Cheung ST, Fan ST and Chen X: Hedgehog signaling in human hepatocellular carcinoma. Cancer Biol Ther. 5:111–117. 2006. View Article : Google Scholar : PubMed/NCBI | |
Fu X, Wang Q, Chen X, et al: Expression patterns and polymorphisms of PTCH in Chinese hepatocellular carcinoma patients. Exp Mol Pathol. 84:195–199. 2008. View Article : Google Scholar : PubMed/NCBI | |
Sicklick JK, Li YX, Jayaraman A, et al: Dysregulation of the Hedgehog pathway in human hepatocarcinogenesis. Carcinogenesis. 27:748–757. 2006. View Article : Google Scholar : PubMed/NCBI | |
Katoh Y and Katoh M: Integrative genomic analyses on GLI2: mechanism of Hedgehog priming through basal GLI2 expression, and interaction map of stem cell signaling network with P53. Int J Oncol. 33:881–886. 2008.PubMed/NCBI | |
He J, Sheng T, Stelter AA, et al: Suppressing Wnt signaling by the hedgehog pathway through sFRP-1. J Biol Chem. 281:35598–35602. 2006. View Article : Google Scholar : PubMed/NCBI | |
Liu YJ, Wang Q, Li W, et al: Rab23 is a potential biological target for treating hepatocellular carcinoma. World J Gastroenterol. 13:1010–1017. 2007. View Article : Google Scholar : PubMed/NCBI | |
Omenetti A and Diehl AM: The adventures of sonic hedgehog in development and repair. II Sonic hedgehog and liver development, inflammation, and cancer. Am J Physiol Gastrointest Liver Physiol. 294:G595–G598. 2008. View Article : Google Scholar : PubMed/NCBI | |
de Pereira TA, Witek RP, Syn WK, et al: Viral factors induce Hedgehog pathway activation in humans with viral hepatitis, cirrhosis, and hepatocellular carcinoma. Lab Invest. 90:1690–1703. 2010.PubMed/NCBI | |
Eichenmuller M, Gruner I, Hagl B, et al: Blocking the hedgehog pathway inhibits hepatoblastoma growth. Hepatology. 49:482–490. 2009. View Article : Google Scholar : PubMed/NCBI | |
Suzuki A, Sekiya S, Onishi M, et al: Flow cytometric isolation and clonal identification of self-renewing bipotent hepatic progenitor cells in adult mouse liver. Hepatology. 48:1964–1978. 2008. View Article : Google Scholar : PubMed/NCBI | |
Rountree CB, Ding W, He L and Stiles B: Expansion of CD133-expressing liver cancer stem cells in liver-specific phosphatase and tensin homolog deleted on chromosome 10-deleted mice. Stem Cells. 27:290–299. 2009. View Article : Google Scholar : PubMed/NCBI | |
Yin S, Li J, Hu C, et al: CD133 positive hepatocellular carcinoma cells possess high capacity for tumorigenicity. Int J Cancer. 120:1444–1450. 2007. View Article : Google Scholar : PubMed/NCBI | |
Ma S, Chan KW, Hu L, et al: Identification and characterization of tumorigenic liver cancer stem/progenitor cells. Gastroenterology. 132:2542–2556. 2007. View Article : Google Scholar : PubMed/NCBI | |
Suetsugu A, Nagaki M, Aoki H, Motohashi T, Kunisada T and Moriwaki H: Characterization of CD133+ hepatocellular carcinoma cells as cancer stem/progenitor cells. Biochem Biophys Res Commun. 351:820–824. 2006. | |
Kohga K, Tatsumi T, Takehara T, et al: Expression of CD133 confers malignant potential by regulating metalloproteinases in human hepatocellular carcinoma. J Hepatol. 52:872–879. 2010. View Article : Google Scholar : PubMed/NCBI | |
Yao J, Zhang T, Ren J, Yu M and Wu G: Effect of CD133/prominin-1 antisense oligodeoxynucleotide on in vitro growth characteristics of Huh-7 human hepatocarcinoma cells and U251 human glioma cells. Oncol Rep. 22:781–787. 2009.PubMed/NCBI | |
Song W, Li H, Tao K, et al: Expression and clinical significance of the stem cell marker CD133 in hepatocellular carcinoma. Int J Clin Pract. 62:1212–1218. 2008. View Article : Google Scholar : PubMed/NCBI | |
Ma S, Chan KW, Lee TK, et al: Aldehyde dehydrogenase discriminates the CD133 liver cancer stem cell populations. Mol Cancer Res. 6:1146–1153. 2008. View Article : Google Scholar : PubMed/NCBI | |
Zhu Z, Hao X, Yan M, et al: Cancer stem/progenitor cells are highly enriched in CD133+CD44+ population in hepatocellular carcinoma. Int J Cancer. 126:2067–2078. 2010.PubMed/NCBI | |
You H, Ding W and Rountree CB: Epigenetic regulation of cancer stem cell marker CD133 by transforming growth factor-beta. Hepatology. 51:1635–1644. 2010. View Article : Google Scholar : PubMed/NCBI | |
Ma S, Lee TK, Zheng BJ, Chan KW and Guan XY: CD133+ HCC cancer stem cells confer chemoresistance by preferential expression of the Akt/PKB survival pathway. Oncogene. 27:1749–1758. 2008. | |
Ma S, Tang KH, Chan YP, et al: miR-130b promotes CD133(+) liver tumor-initiating cell growth and self-renewal via tumor protein 53-induced nuclear protein 1. Cell Stem Cell. 7:694–707. 2010.PubMed/NCBI | |
Salnikov AV, Kusumawidjaja G, Rausch V, et al: Cancer stem cell marker expression in hepatocellular carcinoma and liver metastases is not sufficient as single prognostic parameter. Cancer Lett. 275:185–193. 2009. View Article : Google Scholar : PubMed/NCBI | |
Schmelzer E and Reid LM: EpCAM expression in normal, non-pathological tissues. Front Biosci. 13:3096–3100. 2008. View Article : Google Scholar : PubMed/NCBI | |
Kimura O, Takahashi T, Ishii N, et al: Characterization of the epithelial cell adhesion molecule (EpCAM)+ cell population in hepatocellular carcinoma cell lines. Cancer Sci. 101:2145–2155. 2010. View Article : Google Scholar : PubMed/NCBI | |
Ji J, Yamashita T, Budhu A, et al: Identification of microRNA-181 by genome-wide screening as a critical player in EpCAM-positive hepatic cancer stem cells. Hepatology. 50:472–480. 2009. View Article : Google Scholar : PubMed/NCBI | |
Arzumanyan A, Friedman T, Ng IO, Clayton MM, Lian Z and Feitelson MA: Does the hepatitis B antigen HBx promote the appearance of liver cancer stem cells? Cancer Res. 71:3701–3708. 2011. View Article : Google Scholar : PubMed/NCBI | |
Lu TY, Lu RM, Liao MY, et al: Epithelial cell adhesion molecule regulation is associated with the maintenance of the undifferentiated phenotype of human embryonic stem cells. J Biol Chem. 285:8719–8732. 2010. View Article : Google Scholar : PubMed/NCBI | |
Goodell MA, Brose K, Paradis G, Conner AS and Mulligan RC: Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Exp Med. 183:1797–1806. 1996. View Article : Google Scholar : PubMed/NCBI | |
Ding XW, Wu JH and Jiang CP: ABCG2: a potential marker of stem cells and novel target in stem cell and cancer therapy. Life Sci. 86:631–637. 2010. View Article : Google Scholar : PubMed/NCBI | |
Chiba T, Kita K, Zheng YW, et al: Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties. Hepatology. 44:240–251. 2006. View Article : Google Scholar : PubMed/NCBI | |
Shi GM, Xu Y, Fan J, et al: Identification of side population cells in human hepatocellular carcinoma cell lines with stepwise metastatic potentials. J Cancer Res Clin Oncol. 134:1155–1163. 2008. View Article : Google Scholar : PubMed/NCBI | |
Zhang N, Li R, Tao KS, et al: Characterization of a stem-like population in hepatocellular carcinoma MHCC97 cells. Oncol Rep. 23:827–831. 2010.PubMed/NCBI | |
Kamohara Y, Haraguchi N, Mimori K, et al: The search for cancer stem cells in hepatocellular carcinoma. Surgery. 144:119–124. 2008. View Article : Google Scholar : PubMed/NCBI | |
Qiang GH, Yu DC and Jiang CP: Side population cells and liver cancer stem cells. World Chin J Digestol. 18:971–974. 2010.(In Chinese). | |
Polgar O, Robey RW and Bates SE: ABCG2: structure, function and role in drug response. Expert Opin Drug Metab Toxicol. 4:1–15. 2008. View Article : Google Scholar : PubMed/NCBI | |
Sarkadi B, Ozvegy-Laczka C, Nemet K and Varadi A: ABCG2 - a transporter for all seasons. FEBS Lett. 567:116–120. 2004. View Article : Google Scholar : PubMed/NCBI | |
Han B and Zhang JT: Multidrug resistance in cancer chemotherapy and xenobiotic protection mediated by the half ATP-binding cassette transporter ABCG2. Curr Med Chem Anticancer Agents. 4:31–42. 2004. View Article : Google Scholar : PubMed/NCBI | |
Zen Y, Fujii T, Yoshikawa S, et al: Histological and culture studies with respect to ABCG2 expression support the existence of a cancer cell hierarchy in human hepatocellular carcinoma. Am J Pathol. 170:1750–1762. 2007. View Article : Google Scholar | |
Xi Z, Jiang CP and Ding YT: Expression of stem cell marker ABCG2 and its significance in hepatocellular carcinoma tissue and cell lines. World Chin J Digestol. 17:247–252. 2009. | |
Hu C, Li H, Li J, et al: Analysis of ABCG2 expression and side population identifies intrinsic drug efflux in the HCC cell line MHCC-97L and its modulation by Akt signaling. Carcinogenesis. 29:2289–2297. 2008. View Article : Google Scholar : PubMed/NCBI | |
Yang ZF, Ngai P, Ho DW, et al: Identification of local and circulating cancer stem cells in human liver cancer. Hepatology. 47:919–928. 2008. View Article : Google Scholar : PubMed/NCBI | |
Yang ZF, Ho DW, Ng MN, et al: Significance of CD90+ cancer stem cells in human liver cancer. Cancer Cell. 13:153–166. 2008. | |
Haraguchi N, Ishii H, Mimori K, et al: CD13 is a therapeutic target in human liver cancer stem cells. J Clin Invest. 120:3326–3339. 2010. View Article : Google Scholar : PubMed/NCBI | |
Oliva J, French BA, Qing X and French SW: The identification of stem cells in human liver diseases and hepatocellular carcinoma. Exp Mol Pathol. 88:331–340. 2010. View Article : Google Scholar : PubMed/NCBI | |
Martinez-Chantar ML, Lu SC, Mato JM, et al: The role of stem cells/progenitor cells in liver carcinogenesis in glycine N-methyltransferase deficient mice. Exp Mol Pathol. 88:234–237. 2010. View Article : Google Scholar : PubMed/NCBI | |
Andersen JB, Loi R, Perra A, et al: Progenitor-derived hepatocellular carcinoma model in the rat. Hepatology. 51:1401–1409. 2010. View Article : Google Scholar : PubMed/NCBI | |
Kim H, Choi GH, Na DC, et al: Human hepatocellular carcinomas with ‘stemness’-related marker expression: keratin 19 expression and a poor prognosis. Hepatology. 54:1707–1717. 2011. | |
Yang W, Yan HX, Chen L, et al: Wnt/beta-catenin signaling contributes to activation of normal and tumorigenic liver progenitor cells. Cancer Res. 68:4287–4295. 2008. View Article : Google Scholar : PubMed/NCBI | |
Xie Z, Choong PF, Poon LF, et al: Inhibition of CD44 expression in hepatocellular carcinoma cells enhances apoptosis, chemosensitivity, and reduces tumorigenesis and invasion. Cancer Chemother Pharmacol. 62:949–957. 2008. View Article : Google Scholar : PubMed/NCBI | |
Yu F, Hao X, Zhao H, et al: Delta-like 1 contributes to cell growth by increasing the interferon-inducible protein 16 expression in hepatocellular carcinoma. Liver Int. 30:703–714. 2010. View Article : Google Scholar : PubMed/NCBI | |
Machida K, Tsukamoto H, Mkrtchyan H, et al: Toll-like receptor 4 mediates synergism between alcohol and HCV in hepatic oncogenesis involving stem cell marker Nanog. Proc Natl Acad Sci USA. 106:1548–1553. 2009. View Article : Google Scholar : PubMed/NCBI | |
Knight B, Tirnitz-Parker JE and Olynyk JK: C-kit inhibition by imatinib mesylate attenuates progenitor cell expansion and inhibits liver tumor formation in mice. Gastroenterology. 135:969–979. 2008. View Article : Google Scholar : PubMed/NCBI | |
Okamura D, Ohtsuka M, Kimura F, et al: Ezrin expression is associated with hepatocellular carcinoma possibly derived from progenitor cells and early recurrence after surgical resection. Mod Pathol. 21:847–855. 2008. View Article : Google Scholar | |
Jabari S, Meissnitzer M, Quint K, et al: Cellular plasticity of trans- and dedifferentiation markers in human hepatoma cells in vitro and in vivo. Int J Oncol. 35:69–80. 2009.PubMed/NCBI | |
Yu J, Vodyanik MA, Smuga-Otto K, et al: Induced pluripotent stem cell lines derived from human somatic cells. Science. 318:1917–1920. 2007. View Article : Google Scholar : PubMed/NCBI | |
Zhong X, Li N, Liang S, Huang Q, Coukos G and Zhang L: Identification of microRNAs regulating reprogramming factor LIN28 in embryonic stem cells and cancer cells. J Biol Chem. 285:41961–41971. 2010. View Article : Google Scholar : PubMed/NCBI | |
Viswanathan SR, Powers JT, Einhorn W, et al: Lin28 promotes transformation and is associated with advanced human malignancies. Nat Genet. 41:843–848. 2009. View Article : Google Scholar : PubMed/NCBI | |
Yang X, Lin X, Zhong X, et al: Double-negative feedback loop between reprogramming factor LIN28 and microRNA let-7 regulates aldehyde dehydrogenase 1-positive cancer stem cells. Cancer Res. 70:9463–9472. 2010. View Article : Google Scholar : PubMed/NCBI | |
Smith LM, Nesterova A, Ryan MC, et al: CD133/prominin-1 is a potential therapeutic target for antibody-drug conjugates in hepatocellular and gastric cancers. Br J Cancer. 99:100–109. 2008. View Article : Google Scholar : PubMed/NCBI | |
Wang L, Su W, Liu Z, et al: CD44 antibody-targeted liposomal nanoparticles for molecular imaging and therapy of hepatocellular carcinoma. Biomaterials. 33:5107–5114. 2012. View Article : Google Scholar : PubMed/NCBI | |
Fan ST, Yang ZF, Ho DW, Ng MN, Yu WC and Wong J: Prediction of posthepatectomy recurrence of hepatocellular carcinoma by circulating cancer stem cells: a prospective study. Ann Surg. 254:569–576. 2011. View Article : Google Scholar : PubMed/NCBI |