TGF β1 mediates epithelial mesenchymal transition via β6 integrin signaling pathway in breast cancer

Cancer Invest. 2014 Oct;32(8):409-15. doi: 10.3109/07357907.2014.933235. Epub 2014 Jul 14.

Abstract

Background: To understand the function of β6 integrin and elucidate its signaling pathways in TGF-β-induced EMT in breast cancer.

Methods: The interactions between TGF-β1 and β6 integrin were measured by coimmunoprecipitation. The EMT responses, phospherlation of PI3K/Akt and COX-2 expression were determined by real-time PCR, transwell assay, and western blot after the blockage of β6 integrin.

Results: TGF-β1 and β6 integrin could bind with each other. Blockage of β6 integrin rescued TGF-β1-induced EMT phenotype and reduced expression of COX-2 via dephosphorylation of PI3K/Akt.

Conclusions: β6 integrin plays a critical role in TGF-β1-induced EMT and overexpression of COX-2 in breast cancer.

Keywords: Breast carcinoma; COX-2; EMT; PI3K pathways; TGF-β; β6 integrin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cyclooxygenase 2 / biosynthesis
  • Cyclooxygenase 2 / metabolism
  • Epithelial-Mesenchymal Transition
  • Female
  • Humans
  • Immunoprecipitation
  • Integrin beta Chains / genetics
  • Integrin beta Chains / metabolism*
  • MCF-7 Cells
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • Transfection
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism*

Substances

  • Integrin beta Chains
  • Transforming Growth Factor beta1
  • integrin beta6
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt