Zhong Li
Shanghai Institute of Cell Therapy, China
Title: A splicing variant of merlin promotes metastasisin hepatocellular carcinoma
Biography
Biography: Zhong Li
Abstract
Merlin (moesin-ezrin-radixin-like protein), encoded by the neurofibromatosis type 2 (Nf2) tumor suppressor gene, is a member of the band 4.1 family. As one of the most versatile tumor suppressors, it is capable of integrating several different mechanisms that regulate cell proliferation, motility, survival and signaling pathways. As we know, Merlin has at least five splicing forms. However, little is known about the functional importance of these splicing forms. To understand the roles of Merlin in the process of tumorigenesis and tumor metastasis, we studied Merlin and its splicing forms in hepatocellular carcinoma (HCC). Our data shows that Merlin is present at low levels in HCC specimen, particularly in metastatic tumors, where it is associated with a poor prognosis. Surprisingly, a splicing variant of Merlin that lacks exons 2, 3 and 4 (ï„2–4Merlin) is amplified in HCC and portal vein tumor thrombus (PVTT) specimens and in the CSQT2 cell line derived from PVTT. Our studies show that ï„2–4Merlin interferes with the capacity of wild-type Merlin to bind b-catenin and ERM, and it localizes in the cytoplasm rather than at the cell surface. Furthermore, ï„2–4Merlin overexpression increases the expression levels of b-catenin and stemness-related genes , induces the epithelium–mesenchymal-transition phenotype promoting cell migration in vitro and the formation of lung metastasis in vivo. Our results indicate that the ï„2–4Merlin variant disrupts the normal function of Merlin and promotes tumour metastasis.