Src family kinases mediate epidermal growth factor receptor signaling from lipid rafts in breast cancer cells

• DOI: 10.4161/cbt.12.8.16907
• Publication Date: 2011-10-17T14:18:29Z
• Authors: Mary E. Irwin; Natacha Bohin; Julie L. Boerner
• Keywords: Lipid raft; Cyclin-dependent kinase 8

Activation of the epidermal growth factor receptor (EGFR) regulates cellular proliferation, survival, and migration breast cancer cells. In particular, EGFR recruits signaling proteins to cell membrane leading their phosphorylation activation. However, also localizes other structures, including endosomes, mitochondrion, nuclei. Recently, we demonstrated that lipid raft localization in triple-negative lines promotes protein-dependent, kinase-independent activation Akt. Here, further define mechanism by which rafts regulate Specifically, show non-receptor tyrosine kinase c-Src co-localizes co-associates with rafts. Breast cells resistant treatment inhibitors, were Src family (SFK) inhibitors; however, combination SFK inhibitors synergistically decreases viability. We found this decrease viability observed inhibitor co-treatment correlates loss Akt phosphorylation. addition, co-localized rafts, phospho-inositide 3 (PI3K) was associated Together, data herein suggest provide a platform for interaction EGFR, c-Src, PI3K, survival