Filamin A mediates HGF/c-MET signaling in tumor cell migration
2011 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 128, no 4, 839-846 p.Article in journal (Refereed) Published
Deregulated hepatocyte growth factor (HGF)/c-MET axis has been correlated with poor clinical outcome and drug resistance in may human cancers. Identification of novel regulatory mechanisms influencing HGF/c-MET signaling may therefore be necessary to develop more effective cancer therapies. In our study, we show that multiple human cancer tissues and cells express filamin A (FLNA), a large cytoskeletal actin-binding protein, and expression of c-MET is significantly reduced in human tumor cells deficient for FLNA. The FLNA-deficient tumor cells exhibited poor migrative and invasive ability in response to Kg. On the other hand, the anchorage-dependent and independent tumor cell proliferation was not altered by HGF. The FLNA-deficiency specifically attenuated the activation of the c-MET downstream signaling molecule AKT in response to HGF stimulation. Furthermore, FLNA enhanced c-MET promoter activity by its binding to SMAD2. The impact of FLNA deficiency on c-NET expression and HGF-mediated cell migration in human tumor cells was confirmed in primary mouse embryonic fibroblasts deficient for Flna. These data suggest that FLNA is one of the important regulators of c-MET signaling and HGF-induced tumor cell migration.
Place, publisher, year, edition, pages
2011. Vol. 128, no 4, 839-846 p.
Migration, invasion, melanoma cells, fibroblasts
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-148093DOI: 10.1002/ijc.25417ISI: 000286555700011PubMedID: 20473907OAI: oai:DiVA.org:uu-148093DiVA: diva2:401211