Capn4 contributes to tumour growth and metastasis of hepatocellular carcinoma by activation of the FAK-Src signalling pathways

• DOI: 10.1002/path.4395
• Publication Date: 2014-06-24T22:01:15Z
• Authors: Zhi Dai; Shao-Lai Zhou; Zheng-Jun Zhou; Dou-Sheng Bai; Xiao-Yu Xu; Xiu-Tao Fu; Qing Chen; Yi-Ming Zhao; Kai Zhu; Lei Yu; Guo-Huan Yang; Zheng Wang; Wei-Zhong Wu; Jian Zhou; Jia Fan
• Keywords: MMP2; Tissue microarray

Calpain small subunit 1 (Capn4) has been identified as a major gene that promotes metastasis of hepatocellular carcinoma (HCC). However, the mechanism by which Capn4 progression HCC is not understood. In this study, we found expression was increased in highly metastatic cell lines and tumour tissue from patients compared to healthy patient tissue. Over-expression cells enhanced growth vitro invasiveness, tumourigenicity lung vivo. Protein microarray analyses showed multiple proteins regulated Capn4. Interestingly, physically associate with FAK promoted hyperactivity FAK–Src signalling pathway via phosphorylation specific tyrosine residues FAK, Src p130Cas. Knock-down suppressed malignant behaviour inhibited pathway. Furthermore, Capn4-mediated invasion required up-regulation matrix metalloproteinase-2 (MMP2) through activation Our clinical data revealed correlated well levels phospho-FAK, over-expression both phospho-FAK correlates poorest survival outcomes HCC. conclusion, our can contribute MMP2. Copyright © 2014 Pathological Society Great Britain Ireland. Published John Wiley & Sons, Ltd.