Exo70 Isoform Switching Upon Epithelial-mesenchymal Transition Mediates Cancer Cell Invasion

Overview

Journal Dev Cell

Publisher Cell Press

Specialties Cell Biology
Reproductive Medicine

Date 2013 Dec 17

PMID 24331928

Citations 43

Authors

Hezhe Lu

Jianglan Liu

Shujing Liu

Jingwen Zeng

Deqiang Ding

Russ P Carstens

Yusheng Cong

Xiaowei Xu

Wei Guo

Affiliations

Soon will be listed here.

Abstract

Epithelial-mesenchymal transition (EMT) is an important developmental process hijacked by cancer cells for their dissemination. Here, we show that Exo70, a component of the exocyst complex, undergoes isoform switching mediated by ESRP1, a pre-mRNA splicing factor that regulates EMT. Expression of the epithelial isoform of Exo70 affects the levels of key EMT transcriptional regulators such as Snail and ZEB2 and is sufficient to drive the transition to epithelial phenotypes. Differential Exo70 isoform expression in human tumors correlates with cancer progression, and increased expression of the epithelial isoform of Exo70 inhibits tumor metastasis in mice. At the molecular level, the mesenchymal-but not the epithelial-isoform of Exo70 interacts with the Arp2/3 complex and stimulates actin polymerization for tumor invasion. Our findings provide a mechanism by which the exocyst function and actin dynamics are modulated for EMT and tumor invasion.

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