HCRP1 inhibits TGF-β induced epithelial-mesenchymal transition in hepatocellular carcinoma

Yang,Wenlin; Wang,Ji-Gang; Xu,Jiawen; Zhou,Danmei; Ren,Kehan; Hou,Chenjian; Chen,Linlin; Liu,Xiuping

doi:10.3892/ijo.2017.3903

HCRP1 inhibits TGF-β induced epithelial-mesenchymal transition in hepatocellular carcinoma

Authors:
- Wenlin Yang
- Ji-Gang Wang
- Jiawen Xu
- Danmei Zhou
- Kehan Ren
- Chenjian Hou
- Linlin Chen
- Xiuping Liu
View Affiliations

Affiliations: Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, P.R. China, Department of Pathology, Shangdong Provincial Hospital Affiliated to Shangdong University, Jinan, Shandong 250021, P.R. China, Department of Pathology, The Fifth Hospital of Shanghai, Fudan University, Shanghai 200240, P.R. China
Published online on: March 8, 2017 https://doi.org/10.3892/ijo.2017.3903
Pages: 1233-1240

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-related protein 1 (HCRP1), also known as human vacuolar protein sorting 37 homologue A (hVps37A), has not been detected or is significantly downregulated in hepatocellular carcinoma (HCC) tissues. However, information on the regulatory mechanisms of HCRP1 in HCC remains unclear. Here we found that the downregulation of HCRP1 in HepG2 cells (with low invasion capacity) significantly enhanced migration and invasion, whereas HCRP1 upregulation in SMMC-7721 cells (with high invasion capacity) generated the opposite result. Interestingly, the morphology of HepG2 cells significantly changed from an epithelial to mesenchymal phenotype after HCRP1 knockdown. Moreover, we observed a decrease in the expression of epithelial cell markers E-cadherin and β-catenin, and an increase in the expression of mesenchymal cell markers N-cadherin and vimentin. We also observed that the downregulation of HCRP1 induced epithelial-mesenchymal transition (EMT) through the transforming growth factor-β pathway. Together, our findings define a novel function for HCRP1 from the perspective of EMT, which is closely associated with the migration and invasion of HCC cells.

View Figures

View References

1	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI
2	Zhao P, Wang JG, Gao P, Li X and Brewer R: Sudden unexpected death from natural diseases: Fifteen years' experience with 484 cases in Seychelles. J Forensic Leg Med. 37:33–38. 2016. View Article : Google Scholar
3	Meguro M, Mizuguchi T, Kawamoto M and Hirata K: The molecular pathogenesis and clinical implications of hepatocellular carcinoma. Int J Hepatol. 2011:8186722011. View Article : Google Scholar : PubMed/NCBI
4	Thorgeirsson SS and Grisham JW: Molecular pathogenesis of human hepatocellular carcinoma. Nat Genet. 31:339–346. 2002. View Article : Google Scholar : PubMed/NCBI
5	Xu Z, Liang L, Wang H, Li T and Zhao M: HCRP1, a novel gene that is downregulated in hepatocellular carcinoma, encodes a growth-inhibitory protein. Biochem Biophys Res Commun. 311:1057–1066. 2003. View Article : Google Scholar : PubMed/NCBI
6	Wittinger M, Vanhara P, El-Gazzar A, Savarese-Brenner B, Pils D, Anees M, Grunt TW, Sibilia M, Holcmann M, Horvat R, et al: hVps37A Status affects prognosis and cetuximab sensitivity in ovarian cancer. Clin Cancer Res. 17:7816–7827. 2011. View Article : Google Scholar : PubMed/NCBI
7	Perisanidis C, Savarese-Brenner B, Würger T, Wrba F, Huynh A, Schopper C, Kornek G, Selzer E, Ewers R, Psyrri A, et al: HCRP1 expression status is a significant prognostic marker in oral and oropharyngeal cancer. Oral Dis. 19:206–211. 2013. View Article : Google Scholar
8	Xu J, Yang W, Wang Q, Zhang Q, Li X, Lin X, Liu X and Qin Y: Decreased HCRP1 expression is associated with poor prognosis in breast cancer patients. Int J Clin Exp Pathol. 7:7915–7922. 2014.
9	Yang W, Wang JG, Wang Q, Qin Y, Lin X, Zhou D, Ren K, Hou C, Xu J and Liu X: Decreased HCRP1 promotes breast cancer metastasis by enhancing EGFR phosphorylation. Biochem Biophys Res Commun. 477:222–228. 2016. View Article : Google Scholar : PubMed/NCBI
10	Du Y, Wang P, Sun H, Yang J, Lang X, Wang Z, Zang S, Chen L, Ma J and Sun D: HCRP1 is downregulated in non-small cell lung cancer and regulates proliferation, invasion, and drug resistance. Tumour. 37:15893–15901. 2016. View Article : Google Scholar
11	Bache KG, Slagsvold T, Cabezas A, Rosendal KR, Raiborg C and Stenmark H: The growth-regulatory protein HCRP1/hVps37A is a subunit of mammalian ESCRT-I and mediates receptor down-regulation. Mol Biol Cell. 15:4337–4346. 2004. View Article : Google Scholar : PubMed/NCBI
12	Voutsadakis IA: Epithelial-mesenchymal transition (EMT) and regulation of EMT factors by steroid nuclear receptors in breast cancer: A review and in silico investigation. J Clin Med. 5:E112016. View Article : Google Scholar : PubMed/NCBI
13	Wendt MK, Tian M and Schiemann WP: Deconstructing the mechanisms and consequences of TGF-β-induced EMT during cancer progression. Cell Tissue Res. 347:85–101. 2012. View Article : Google Scholar
14	Giannelli G, Koudelkova P, Dituri F and Mikulits W: Role of epithelial to mesenchymal transition in hepatocellular carcinoma. J Hepatol. 65:798–808. 2016. View Article : Google Scholar : PubMed/NCBI
15	van Zijl F, Mall S, Machat G, Pirker C, Zeillinger R, Weinhaeusel A, Bilban M, Berger W and Mikulits W: A human model of epithelial to mesenchymal transition to monitor drug efficacy in hepatocellular carcinoma progression. Mol Cancer Ther. 10:850–860. 2011. View Article : Google Scholar : PubMed/NCBI
16	Kalluri R and Weinberg RA: The basics of epithelial-mesenchymal transition. J Clin Invest. 119:1420–1428. 2009. View Article : Google Scholar : PubMed/NCBI
17	van Zijl F, Zulehner G, Petz M, Schneller D, Kornauth C, Hau M, Machat G, Grubinger M, Huber H and Mikulits W: Epithelial-mesenchymal transition in hepatocellular carcinoma. Future Oncol. 5:1169–1179. 2009. View Article : Google Scholar : PubMed/NCBI
18	Duivenvoorden WC, Hirte HW and Singh G: Transforming growth factor beta1 acts as an inducer of matrix metalloproteinase expression and activity in human bone-metastasizing cancer cells. Clin Exp Metastasis. 17:27–34. 1999. View Article : Google Scholar : PubMed/NCBI
19	Lai MW, Huang SF, Lin SM, Chen TC, Lin CY, Yeh CN, Yeh TS, Chen MF and Yeh CT: Expression of the HCRP1 mRNA in HCC as an independent predictor of disease-free survival after surgical resection. Hepatol Res. 39:164–176. 2009. View Article : Google Scholar : PubMed/NCBI
20	Giannelli G, Villa E and Lahn M: Transforming growth factor-β as a therapeutic target in hepatocellular carcinoma. Cancer Res. 74:1890–1894. 2014. View Article : Google Scholar : PubMed/NCBI