SNF2H promotes hepatocellular carcinoma proliferation by activating the Wnt/β-catenin signaling pathway

Wang,Yanan; Qin,Juanxiu; Liu,Qian; Hong,Xufen; Li,Tianming; Zhu,Yuanjun; He,Lei; Zheng,Bing; Li,Min

doi:10.3892/ol.2016.4681

SNF2H promotes hepatocellular carcinoma proliferation by activating the Wnt/β-catenin signaling pathway

Authors:
- Yanan Wang
- Juanxiu Qin
- Qian Liu
- Xufen Hong
- Tianming Li
- Yuanjun Zhu
- Lei He
- Bing Zheng
- Min Li
View Affiliations

Affiliations: Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200240, P.R. China, Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China
Published online on: June 7, 2016 https://doi.org/10.3892/ol.2016.4681
Pages: 1329-1336
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and has an extremely poor prognosis. Surgical resection is always inapplicable to HCC patients diagnosed at an advanced tumor stage. The mechanisms underlying HCC cell proliferation remain obscure. In the present study, SWItch/sucrose nonfermentable catalytic subunit SNF2 (SNF2H) expression was tested in HCC tissues and Wnt/β-catenin pathway activation upon overexpression of SNF2H or knockdown of SNF2H expression was investigated in cultured HCC cells. It was demonstrated that SNF2H is a vital factor for HCC growth. The SNF2H expression level is increased in HCC tissues compared with paratumoral liver tissues. SNF2H promotes HCC cell proliferation and colony formation ability in vitro. SNF2H may increase the protein level of β‑catenin and enhance its nuclear accumulation in HCC cells, thereby leading to the activation of the Wnt/β‑catenin signaling pathway. In conclusion, the present results indicate that SNF2H plays a vital role in HCC cell growth, suggesting that SNF2H may be a promising therapeutic target for HCC treatment.

View Figures

View References

1	Ferlay J, Shin H, Bray F, Forman D, Mathers C and Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 127:2893–2917. 2010. View Article : Google Scholar : PubMed/NCBI
2	Forner A, Hessheimer AJ, Isabel Real M and Bruix J: Treatment of hepatocellular carcinoma. Crit Rev Oncol Hematol. 60:89–98. 2006. View Article : Google Scholar : PubMed/NCBI
3	Boyault S, Rickman DS, deReyniès A, Balabaud C, Rebouissou S, Jeannot E, Hérault A, Saric J, Belghiti J, Franco D, et al: Transcriptome classification of HCC is related to gene alterations and to new therapeutic targets. Hepatology. 45:42–52. 2007. View Article : Google Scholar : PubMed/NCBI
4	Clevers H: Wnt/beta-catenin signaling in development and disease. Cell. 127:469–480. 2006. View Article : Google Scholar : PubMed/NCBI
5	Takigawa Y and Brown AM: Wnt signaling in liver cancer. Curr Drug Targets. 9:1013–1024. 2008. View Article : Google Scholar : PubMed/NCBI
6	Polakis P: The many ways of Wnt in cancer. Curr Opin Genet Dev. 17:45–51. 2007. View Article : Google Scholar : PubMed/NCBI
7	Valenta T, Hausmann G and Basler K: The many faces and functions of β-catenin. EMBO J. 31:2714–2736. 2012. View Article : Google Scholar : PubMed/NCBI
8	Guigon CJ, Kim DW, Zhu X, Zhao L and Cheng SY: Tumor suppressor action of liganded thyroid hormone receptor beta by direct repression of beta-catenin gene expression. Endocrinology. 151:5528–5536. 2010. View Article : Google Scholar : PubMed/NCBI
9	Li Q, Dashwood WM, Zhong X, Al-Fageeh and Dashwood RH: Cloning of the rat beta-catenin gene (Ctnnb1) promoter and its functional analysis compared with the Catnb and CTNNB1 promoters. Genomics. 83:231–242. 2004. View Article : Google Scholar : PubMed/NCBI
10	Liu G, Jiang S, Wang C, et al: Zinc finger transcription factor 191, directly binding to β-catenin promoter, promotes cell proliferation of hepatocellular carcinoma. Hepatology. 55:1830–1839. 2012. View Article : Google Scholar : PubMed/NCBI
11	Liu Y, Ye X, Zhang JB, et al: PROX1 promotes hepatocellular carcinoma proliferation and sorafenib resistance by enhancing β-catenin expression and nuclear translocation. Oncogene. 34:5524–5535. 2015. View Article : Google Scholar : PubMed/NCBI
12	Mohamed MA, Greif PA, Diamond J, Sharaf O, Maxwell P, Montironi R, Young RA and Hamilton PW: Epigenetic events, remodelling enzymes and their relationship to chromatin organization in prostatic intraepithelial neoplasia and prostatic adenocarcinoma. BJU Int. 99:908–915. 2007. View Article : Google Scholar : PubMed/NCBI
13	Stopka T and Skoultchi AI: The ISWI ATPase Snf2h is required for early mouse development. Proc Natl Acad Sci USA. 100:14097–14102. 2003. View Article : Google Scholar : PubMed/NCBI
14	Reisman D, Glaros S and Thompson EA: The SWI/SNF complex and cancer. Oncogene. 28:1653–1668. 2009. View Article : Google Scholar : PubMed/NCBI
15	Jin Q, Mao X, Li B, Guan S, Yao F and Jin F: Overexpression of SMARCA5 correlates with cell proliferation and migration in breast cancer. Tumour Biol. 36:1895–1902. 2015. View Article : Google Scholar : PubMed/NCBI
16	Stopka T, Zakova D, Fuchs O, Kubrova O, Blafkova J, Jelinek J, Necas E and Zivny J: Chromatin remodeling gene SMARCA5 is dysregulated in primitive hematopoietic cells of acute leukemia. Leukemia. 14:1247–1252. 2000. View Article : Google Scholar : PubMed/NCBI
17	Gigek CO, Lisboa LC, Leal MF, Silva PN, Lima EM, Khayat AS, Assumpção PP, Burbano RR and Smith Mde A: SMARCA5 methylation and expression in gastric cancer. Cancer Invest. 29:162–166. 2011. View Article : Google Scholar : PubMed/NCBI
18	Cui J, Zhou X, Liu Y and Tang Z: Mutation and overexpression of the beta-catenin gene may play an important role in primary hepatocellular carcinoma among Chinese people. J Cancer Res Clin Oncol. 127:577–581. 2001. View Article : Google Scholar : PubMed/NCBI
19	Lai TY, Su CC, Kuo WW, Yeh YL, Kuo WH, Tsai FJ, Tsai CH, Weng YJ, Huang CY and Chen LM: β-catenin plays a key role in metastasis of human hepatocellular carcinoma. Oncol Rep. 26:415–422. 2011.PubMed/NCBI
20	Farazi PA and DePinho RA: Hepatocellular carcinoma pathogenesis: From genes to environment. Nat Rev Cancer. 6:674–687. 2006. View Article : Google Scholar : PubMed/NCBI
21	El-Serag HB and Rudolph KL: Hepatocellular carcinoma: Epidemiology and molecular carcinogenesis. Gastroenterology. 132:2557–2576. 2007. View Article : Google Scholar : PubMed/NCBI
22	Chen L, Chan TH, Yuan YF, et al: CHD1L promotes hepatocellular carcinoma progression and metastasis in mice and is associated with these processes in human patients. J Clin Invest. 120:1178–1191. 2010. View Article : Google Scholar : PubMed/NCBI
23	Liu Y, Zhang JB, Qin Y, et al: PROX1 promotes hepatocellular carcinoma metastasis by way of up-regulating hypoxia-inducible factor 1α expression and protein stability. Hepatology. 58:692–705. 2013. View Article : Google Scholar : PubMed/NCBI
24	Chuma M, Sakamoto M, Yasuda J, Fujii G, Nakanishi K, Tsuchiya A, Ohta T, Asaka M and Hirohashi S: Overexpression of cortactin is involved in motility and metastasis of hepatocellular carcinoma. J Hepatol. 41:629–636. 2004. View Article : Google Scholar : PubMed/NCBI
25	Lau SH, Sham JS, Xie D, Tzang CH, Tang D, Ma N, Hu L, Wang Y, Wen JM, Xiao G, Zhang WM, et al: Clusterin plays an important role in hepatocellular carcinoma metastasis. Oncogene. 25:1242–1250. 2006. View Article : Google Scholar : PubMed/NCBI
26	Sun CK, Ng KT, Sun BS, Ho JW, Lee TK, Ng I, Poon RT, Lo CM, Liu CL, Man K and Fan ST: The significance of proline-rich tyrosine kinase2 (Pyk2) on hepatocellular carcinoma progression and recurrence. Br J Cancer. 97:50–57. 2007. View Article : Google Scholar : PubMed/NCBI
27	Tung-Ping Poon R, Fan ST and Wong J: Risk factors, prevention, and management of postoperative recurrence after resection of hepatocellular carcinoma. Ann Surg. 232:10–24. 2000. View Article : Google Scholar : PubMed/NCBI
28	Yang W, Lu Y, Xu Y, Xu L, Zheng W, Wu Y, Li L and Shen P: Estrogen represses hepatocellular carcinoma (HCC) growth via inhibiting alternative activation of tumor-associated macrophages (TAMs). J Biol Chem. 287:40140–40149. 2012. View Article : Google Scholar : PubMed/NCBI
29	Yang WL, Wei L, Huang WQ, Li R, Shen WY, Liu JY, Xu JM, Li B and Qin Y: Vigilin is overexpressed in hepatocellular carcinoma and is required for HCC cell proliferation and tumor growth. Oncol Rep. 31:2328–2334. 2014.PubMed/NCBI
30	Jiang YF, Yang ZH and Hu JQ: Recurrence or metastasis of HCC: Predictors, early detection and experimental antiangiogenic therapy. World J Gastroenterol. 6:61–65. 2000. View Article : Google Scholar : PubMed/NCBI
31	Schmidt-Ott KM and Barasch J: WNT/beta-catenin signaling in nephron progenitors and their epithelial progeny. Kidney Int. 74:1004–1008. 2008. View Article : Google Scholar : PubMed/NCBI
32	Corona DF, Längst G, Clapier CR, Bonte EJ, Ferrari S, Tamkun JW and Becker PB: ISWI is an ATP-dependent nucleosome remodeling factor. Mol Cell. 3:239–245. 1999. View Article : Google Scholar : PubMed/NCBI
33	VargaWeisz PD and Becker PB: Chromatin-remodeling factors: Machines that regulate? Curr Opin Cell Biol. 10:346–353. 1998. View Article : Google Scholar : PubMed/NCBI