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Tissue transglutaminase regulates β‐catenin signaling through a c‐Src‐dependent mechanism
Author(s) -
Condello Salvatore,
Cao Liyun,
Matei Daniela
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.12-222620
Subject(s) - adherens junction , wnt signaling pathway , catenin , microbiology and biotechnology , cell adhesion , cadherin , signal transduction , beta catenin , proto oncogene tyrosine protein kinase src , epithelial–mesenchymal transition , chemistry , biology , cell , metastasis , cancer , biochemistry , genetics
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/P‐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.—Condello, S., Cao, L., Matei, D., Tissue transglutaminase regulates β‐catenin signaling through a c‐Src‐dependent mechanism. FASEB J. 27, 3100–3112 (2013). www.fasebj.org