Epithelial-to-mesenchymal transition and ovarian tumor progression induced by tissue transglutaminase

Minghai Shao, Liyun Cao, Changyu Shen, Minati Satpathy, Bhadrani Chelladurai, Robert M. Bigsby, Harikrishna Nakshatri, Daniela Matei

Research output: Contribution to journalArticle

91 Scopus citations

Abstract

Tissue transglutaminase (TG2), an enzyme that catalyzes Ca 2+-dependent aggregation and polymerization of proteins, is overexpressed in ovarian cancer cells and tumors. We previously reported that TG2 facilitates tumor dissemination using an i.p. xenograft model. Here we show that TG2 modulates epithelial-to-mesenchymal transition (EMT), contributing to increased ovarian cancer cell invasiveness and tumor metastasis. By using stable knockdown and overexpression in epithelial ovarian cancer cells, we show that TG2 induces a mesenchymal phenotype, characterized by cadherin switch and invasive behavior in a Matrigel matrix. This is mediated at the transcriptional level by altering the expression levels and function of several transcriptional repressors, including Zeb1. One mechanism through which TG2 induces Zeb1 is by activating the nuclear factor-κB complex. The effects of TG2 on ovarian cancer cell phenotype and invasiveness translate into increased tumor formation and metastasis in vivo, as assessed by an orthotopic ovarian xenograft model. Highly expressed in ovarian tumors, TG2 promotes EMT and enhances ovarian tumor metastasis by activating oncogenic signaling.

Original languageEnglish (US)
Pages (from-to)9192-9201
Number of pages10
JournalCancer Research
Volume69
Issue number24
DOIs
StatePublished - Dec 15 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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