Alpha 6 beta 4 and alpha 6 beta 1 integrins associate with ErbB-2 in human carcinoma cell lines.
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 (alpha 6 beta 1 and alpha 6 beta 4) with ErbB-2 tyrosine kinase in human carcinoma cell lines. We demonstrated that the alpha 6 beta 4 and alpha 6 beta 1 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 alpha 6 integrin subunit showed a ligand-dependent increase of ErbB-2-phosphorylated molecules coprecipitated with integrins and an increased DNA synthesis. The interaction between growth factor receptors and integrins was also studied in NIH3T3 cells overexpressing alpha 6 beta 4 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 alpha 6 beta 4 integrin and ErbB-2 receptor interaction might contribute to generate a more malignant phenotype in carcinoma cells.
Falcioni
R
R
Laboratorio Oncogenesi Molecolare, Istituto Regina Elena, Centro Ricerca Sperimentale, Rome, Italy. Falcioni@dotto.ifo.it
Antonini
A
A
Nisticò
P
P
Di Stefano
S
S
Crescenzi
M
M
Natali
P G
PG
Sacchi
A
A
D016475:3T3 Cells / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001943:Breast Neoplasms; D002455:Cell Division / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D039121:Integrin alpha6beta1; D039161:Integrin alpha6beta4; D016023:Integrins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms; D010766:Phosphorylation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D017474:Receptors, Laminin / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D039121:Integrin alpha6beta1; D039161:Integrin alpha6beta4; D016023:Integrins; D008024:Ligands; D018719:Erb-b2 Receptor Tyrosine Kinases; D017474:Receptors, Laminin; D013936:Thymidine