Tissue Transglutaminase Regulates β-catenin Signaling Through a C-Src-dependent Mechanism

Overview

Journal FASEB J

Specialties Biology
Physiology

Date 2013 May 4

PMID 23640056

Citations 32

Authors

Salvatore Condello

Liyun Cao

Daniela Matei

Affiliations

Soon will be listed here.

Abstract

Tissue transglutaminase (TG2) is a multifunctional enzyme involved in protein cross-linking and cell adhesion to fibronectin (FN). In cancer, TG2 induces an epithelial to mesenchymal transition, contributing to metastasis. Because cadherins bind β-catenin at cell-cell junctions, disruption of adherens junctions destabilizes cadherin-catenin complexes. The goal of the present study was to analyze whether and how TG2 interacts with and regulates β-catenin signaling in ovarian cancer (OC) cells. We observed a significant correlation between TG2 and β-catenin expression levels in OC cells and tumors. TG2 augmented Wnt/β-catenin signaling, as evidenced by enhanced β-catenin transcriptional activity, inducing transcription of target genes cyclin D1 and c-Myc. By promoting integrin-mediated cell adhesion to FN, TG2 physically associates with and recruits c-Src, which in turn phosphorylates β-catenin at Tyr(654), releasing it from E-cadherin and rendering it available for transcriptional regulation. By interacting with FN and enhancing β-catenin signaling, complexed TG2 stimulates OC cell proliferation. In summary, our data demonstrate that TG2 regulates β-catenin expression and function in OC cells and define the c-Src-dependent mechanism through which this occurs.

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