Tyrosine phosphorylation profiling reveals the signaling network characteristics of Basal breast cancer cells
Basal breast cancer represents an aggressive disease subtype that lacks effective targeted therapies. Global profiling of tyrosine phosphorylation events revealed that basal breast cancer cells are characterized by a SRC family kinase (SFK) signalling network that features LYN, canonical SFK substrates with key roles in cell adhesion and migration, and the receptor tyrosine kinases EGFR and MET. High LYN expression in breast cancer patients was associated with the basal phenotype and poor prognosis, and LYN knockdown blocked invasion of basal breast cancer cells. Combinatorial use of inhibitors directed against SFKs, EGFR or MET achieved greater attenuation of cell proliferation and survival than single agent treatments, consistent with concomitant activation of these kinases. These findings provide novel insights into the biology of basal breast cancers, and highlight multiple kinases and substrates for further evaluation as therapeutic targets and biomarkers.
|Authors||Hochgrafe, F.; Zhang, L.; O'Toole, S. A.; Browne, B. C.; Pinese, M.; Porta Cubas, A.; Lehrbach, G. M.; Croucher, D. R.; Rickwood, D.; Boulghourjian, A.; Shearer, R.; Nair, R.; Swarbrick, A.; Faratian, D.; Mullen, P.; Harrison, D. J.; Biankin, A. V.; Sutherland, R. L.; Raftery, M. J.; Daly, R. J.|
|Publisher Name||CANCER RESEARCH|
|DOI||0008-5472.CAN-10-0911 [pii] 10.1158/0008-5472.CAN-10-0911|
|URL link to publisher's version||http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20861192|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/10515|