HSP4 triggers epithelial‐mesenchymal transition and promotes motility capacities of hepatocellular carcinoma cells via activating AKT

• DOI: 10.1111/liv.14410
• Publication Date: 2020-02-20T13:22:05Z
• Authors: Peng Ma; Wei‐Guo Tang; Jin‐Wu Hu; Ying Hao; Liang‐Kun Xiong; Mao‐Ming Wang; Hao Liu; Wen‐Hui Bo; Kai‐Huan Yu
• Keywords: 0303 health sciences; Carcinoma, Hepatocellular; Epithelial-Mesenchymal Transition; Liver Neoplasms; HSP40 Heat-Shock Proteins; Gene Expression Regulation, Neoplastic; 03 medical and health sciences; Cell Movement; Cell Line, Tumor; Humans; Proto-Oncogene Proteins c-akt; Cell Proliferation; Signal Transduction

Abstract Background and Aims Heat shock factor (HSF4) plays a vital role in carcinogenesis tumour progression. However, its clinical significance implications hepatocellular carcinoma (HCC) remained elusive. Methods RT‐PCR western blot were used to detect the HSF4 expression levels HCC cells tissues. Immunohistochemistry staining was performed on tissue microarray containing 104 patients received radical resection. In vitro effects of proliferation, migration invasion determined by colony formation transwell assays HCCLM3, Huh7, MHCC97L SMMC7721 cells. Epithelial‐mesenchymal transition (EMT) identified RT‐PCR, WB immunofluorescence HCCLM3 AKT pathway activation detected dual luciferase report system Results higher primary tissues derived from recurrent patients, positively correlated with invasiveness potentials cell lines. Clinically, high had significant poorer prognosis. experiments showed silencing inhibited invasion, whereas overexpression inverse effects. Moreover, silence induced an epithelial‐like phenotype, resulted mesenchymal‐like phenotype activating pathway. Further that could activate hypoxia‐inducible factor‐1α (HIF‐1α) dependent, but transforming growth factor‐β (TGF‐β) independent manner. Conclusions is upregulated HCC, resulting greater capacities. promising predictive indicator poor outcome after may promote aggressive behaviour enhancing EMT through HIF1α‐dependent