The role of Cyr61 and LASP1 in growth and metastasis of human hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world with poor prognosis associated with tumor invasion and metastasis. Here we report that two genes - Cyr61 and Lasp1 may play important roles in growth and metastasis of HCC. As a secreted extracellular matrix (ECM)-associated protein, Cyr61 was down-regulated in both HCC tumor tissue and cell lines. Over-expression of Cyr61 suppressed cell proliferation through p53 dependent as well as alternative pathways. Moreover, Cyr61 inhibited cell migration and invasion by interfering with ECM-integrin signaling pathways. In contrast, the focal adhesion scaffolding protein Lasp1 was found to be up-regulated in HCC. Knockdown of Lasp1 by siRNA significantly inhibited cell growth. Alterations in Lasp1 expression inhibited cell migration and invasion, possibly through influencing F-actin dynamics. More interestingly, Lasp1 is transcriptionally regulated and suppressed by p53 binding to its promoter. This work provides new insights into the role of p53 in tumor metastasis.