Tissue transglutaminase expression promotes cell attachment, invasion and survival in breast cancer cells

L. S. Mangala, J. Y. Fok, I. R. Zorrilla-Calancha, A. Verma, K. Mehta

Research output: Contribution to journalArticle

114 Scopus citations

Abstract

Distant metastasis is frequently observed in patients with breast cancer and is a major cause of cancer-related deaths in these patients. Currently, very little is known about the mechanisms that underlie the development of the metastatic phenotype in breast cancer cells. We previously found that metastatic breast cancer cells express high levels of tissue transglutaminase (TG2), but established no direct link between TG2 and metastasis. In this study, we hypothesized that TG2 plays a role in conferring the metastatic phenotype to breast cancer cells. The results obtained suggested that increased expression of TG2 in breast cancer cells contributes to their increased survival, invasion and motility. We further found that TG2 protein in a metastatic breast cancer MDA-MB231 cells was present on the cell surface in close association with integrins β1, β4 and β5. Downregulation of endogenous TG2 by small interfering RNA inhibited fibronectin (Fn)-mediated cell attachment, survival and invasion. Conversely, ectopic expression of TG2 augmented invasion of breast cancer cells and attachment to Fn-coated surfaces. We conclude that TG2 expression in breast cancer cells plays an important role in the development of the metastatic phenotype.

Original languageEnglish (US)
Pages (from-to)2459-2470
Number of pages12
JournalOncogene
Volume26
Issue number17
DOIs
StatePublished - Apr 12 2007

Keywords

  • Cell migration
  • Fibronectin
  • Integrins
  • Invasion
  • Metastasis
  • Transglutaminase

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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