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Signalling involving MET and FAK supports cell division independent of the activity of the cell cycle-regulating CDK4/6 kinases

2019; Springer Nature; Volume: 38; Issue: 30 Linguagem: Inglês

10.1038/s41388-019-0850-2

1476-5594

Chi Zhang, Simon R. Stockwell, May Elbanna, Robin Ketteler, Jamie Freeman, Bissan Al‐Lazikani, Suzanne A. Eccles, Alexis de Haven Brandon, Florence I. Raynaud, Angela Hayes, Paul A. Clarke, Paul Workman, Sibylle Mittnacht,

Microtubule and mitosis dynamics

Deregulation of cyclin-dependent kinases 4 and 6 (CDK4/6) is highly prevalent in cancer; yet, inhibitors against these kinases are currently used only in restricted tumour contexts. The extent to which cancers depend on CDK4/6 and the mechanisms that may undermine such dependency are poorly understood. Here, we report that signalling engaging the MET proto-oncogene receptor tyrosine kinase/focal adhesion kinase (FAK) axis leads to CDK4/6-independent CDK2 activation, involving as critical mechanistic events loss of the CDKI p21