alpha6beta4 integrin and the Met receptor for HGF have been shown independently to promote invasive growth. We demonstrate here that Met selectively associates with alpha6beta4. In carcinoma cells expressing Met alone, HGF does not exert significant biological effects. Ectopic expression of alpha6beta4 restores HGF-regulated processes. Following Met activation, alpha6beta4 is tyrosine phosphorylated and combines with Shc and PI3K, generating an additional signaling platform that potentiates HGF-triggered activation of Ras- and PI3K-dependent pathways. In the presence of an alpha6beta4 mutant defective for Shc recruitment, Met cannot sustain HGF-mediated responses. Surprisingly, a truncated beta4 unable to bind laminins retains the activity of wild-type alpha6beta4. Such findings invoke an unexpected role for alpha6beta4 in cancer invasion as a functional amplifier of biochemical outputs rather than a mechanical adhesive device.
Pubmed ID: 11733063 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Commercial organism provider selling mice, rats and other model animals. American corporation specializing in a variety of pre-clinical and clinical laboratory services for the pharmaceutical, medical device and biotechnology industries. It also supplies assorted biomedical products and research and development outsourcing services for use in the pharmaceutical industry. (Wikipedia)
View all literature mentions