α6β4 and α6β1 integrins associate with ErbB-2 in human carcinoma cell lines

Rita Falcioni, Annalisa Antonini, Paola Nisticò, Stefania Di Stefano, Marco Crescenzi, Pier Giorgio Natali, Ada Sacchi

Research output: Contribution to journalArticlepeer-review

Abstract

Growth factors modulate integrin-mediated cell adhesion and motility, and their receptors are thought to share proteins that mediate intracellular signaling with integrin receptors. The crosstalk between these receptors is thought to play a relevant role in transformation and tumor progression. To highlight possible interactions between growth factors and cell adhesion receptors we investigated whether integrins associate with tyrosine kinase receptors in tumor cells. By affinity chromatography and Western blot analyses of purified immune complexes, we studied the association of laminin receptors (α6β1 and α6β4) with ErbB-2 tyrosine kinase in human carcinoma cell lines. We demonstrated that the α6β4 and α6β1 integrins coprecipitated with ErbB-2 in lysates from carcinoma or NIH3T3 cells overexpressing ErbB-2. Integrin-mediated activation of ErbB-2 receptors suggested that this association is functionally meaningful. Indeed, carcinoma cells treated with a monoclonal antibody to the α6 integrin subunit showed a ligand-dependent increase of ErbB-2-phosphorylated molecules coprecipitated with integrins andan increased DNA synthesis. The interaction between growth factor receptors and integrins was also studied in NIH3T3 cells overexpressing α6β4 receptors and ErbB-2 protein. We report that cells overexpressing both receptors, but not those overexpressing a crippled ErbB- 2, showed enhanced proliferation rates and invasiveness, further suggesting that α6β4 integrin and ErbB-2 receptor interaction might contribute to generate a more malignant phenotype in carcinoma cells.

Original languageEnglish
Pages (from-to)76-85
Number of pages10
JournalExperimental Cell Research
Volume236
Issue number1
DOIs
Publication statusPublished - Oct 10 1997

ASJC Scopus subject areas

  • Cell Biology

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