Tissue transglutaminase regulates β-catenin signaling through a c-Src-dependent mechanism

Salvatore Condello, Liyun Cao, Daniela Matei

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

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 Tyr654, 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.

Original languageEnglish (US)
Pages (from-to)3100-3112
Number of pages13
JournalFASEB Journal
Volume27
Issue number8
DOIs
StatePublished - Aug 2013

Keywords

  • EMT
  • Fibronectin
  • Integrin
  • Wnt signaling

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology
  • Medicine(all)

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