The Human Adenocarcinoma-associated Gene, AGR2, Induces Expression of Amphiregulin Through Hippo Pathway Co-activator YAP1 Activation

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2011 Apr 2

PMID 21454516

Citations 48

Authors

Aiwen Dong

Aparna Gupta

Reetesh K Pai

May Tun

Anson W Lowe

Affiliations

Soon will be listed here.

Abstract

Anterior Gradient Homolog 2 (AGR2) is expressed by the normal intestine and by most human adenocarcinomas, including those derived from the esophagus, pancreas, lung, breast, ovary, and prostate. Xenografts of human adenocarcinoma cell lines in nude mice previously demonstrated that AGR2 supports tumor growth. In addition, AGR2 is able to induce in vitro a transformed phenotype in fibroblast and epithelial cell lines. The mechanism underlying the growth promoting effects of AGR2 is unknown. The present study shows that AGR2 induces expression of amphiregulin (AREG), a growth promoting EGFR ligand. Induced AREG expression in adenocarcinoma cells is able to rescue the transformed phenotype that is lost when AGR2 expression is reduced. Additional experiments demonstrate that AGR2 induction of AREG is mediated by activation of the Hippo signaling pathway co-activator, YAP1. Thus AGR2 promotes growth by regulating the Hippo and EGF receptor signaling pathways.

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