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Src‐dependent autophagic degradation of Ret in FAK‐signalling‐defective cancer cells
Author(s) -
Sandilands Emma,
Serrels Bryan,
Wilkinson Simon,
Frame Margaret C
Publication year - 2012
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2012.92
Subject(s) - proto oncogene tyrosine protein kinase src , focal adhesion , autophagy , microbiology and biotechnology , tyrosine kinase , cancer cell , cancer research , kinase , sh3 domain , phosphorylation , receptor tyrosine kinase , biology , chemistry , signal transduction , cancer , biochemistry , apoptosis , genetics
We have recently described that autophagic targeting of Src maintains cancer cell viability when FAK signalling is defective. Here, we show that the Ret tyrosine kinase is also degraded by autophagy in cancer cells with altered/reduced FAK signalling, preventing its binding to FAK at integrin adhesions. Inhibition of autophagy restores Ret localization to focal adhesions. Importantly, Src kinase activity is required to target Ret to autophagosomes and enhance Ret degradation. Src is thus a general mediator of selective autophagic targeting of adhesion‐linked kinases, and Ret a second FAK‐binding tyrosine kinase degraded through autophagy in cancer cells under adhesion stress. Src—by controlling not only its own degradation but also that of other FAK‐binding partners—allows cancer cell survival, suggesting a new therapeutic strategy.