Epimorphin promotes human hepatocellular carcinoma invasion and metastasis through activation of focal adhesion kinase/extracellular signal-regulated kinase/matrix metalloproteinase-9 axis

• DOI: 10.1002/hep.24562
• Publication Date: 2011-07-11T17:29:25Z
• Authors: Ya-Li Jia; Lei Shi; Jun-Nian Zhou; Chun-Jiang Fu; Lin Chen; Hong-Feng Yuan; Yun-Fang Wang; Xin-Long Yan; Ying-Chen Xu; Quan Zeng; Wen Yue; Xue-Tao Pei
• Keywords: Hepatic stellate cell

The high incidence rate of hepatocellular carcinoma (HCC) is mainly the result frequent metastasis and tumor recurrence. Unfortunately, underlying molecular mechanisms driving HCC are still not fully understood. It has been demonstrated that stroma cells contribute to primary growth metastasis. Within environment, activated hepatic stellate (HSCs) can release a number molecules enhance cancer cell proliferation invasiveness in paracrine manner. Here, for first time, we demonstrate epimorphin (EPM; also called syntaxin-2), an extracellular protein, strongly elevated HSCs within stroma. We show knockdown EPM expression substantially abolishes their effects on invasion Ectopic enhances invasiveness; expressing have markedly increased potential. Furthermore, EPM-mediated found require up-regulation matrix metalloproteinase-9 (MMP-9) through activation focal adhesion kinase (FAK)/extracellular signal-regulated (ERK) axis.Our results EPM, secreted by stroma, promotes activating MMP-9 FAK-ERK pathway.