Beta 4 integrin amplifies ErbB2 signaling to promote mammary tumorigenesis. Academic Article uri icon

Overview

abstract

  • Amplification of the ErbB2 locus, which encodes a receptor tyrosine kinase, is common in aggressive breast tumors and correlates with poor prognosis. The mechanisms underlying ErbB2-mediated breast carcinoma progression remain incompletely defined. To examine the role of the signaling and cell-adhesion receptor beta 4 integrin during ErbB2-mediated tumorigenesis, we introduced a targeted deletion of the beta 4 signaling domain into a mouse model of ErbB2-induced mammary carcinoma. Loss of beta 4 signaling suppresses mammary tumor onset and invasive growth. Ex vivo studies indicate that beta 4 forms a complex with ErbB2 and enhances activation of the transcription factors STAT3 and c-Jun. STAT3 contributes to disruption of epithelial adhesion and polarity, while c-Jun is required for hyperproliferation. Finally, deletion of the beta 4 signaling domain enhances the efficacy of ErbB2-targeted therapy. These results indicate that beta 4 integrin promotes tumor progression by amplifying ErbB2 signaling and identify beta 4 as a potential target for molecular therapy of breast cancer.

publication date

  • August 11, 2006

Research

keywords

  • Carcinoma
  • Integrin beta4
  • Mammary Neoplasms, Experimental
  • Receptor, ErbB-2
  • Signal Transduction

Identity

Scopus Document Identifier

  • 33746764457

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2006.05.047

PubMed ID

  • 16901783

Additional Document Info

volume

  • 126

issue

  • 3