Cancer Cells Haploinsufficient for ATM Are Sensitized to PARP Inhibitors by MET Inhibition.

ABSTRACT: The MET oncogene encodes a tyrosine kinase (TK) receptor. Its activation protects cells from death but also stimulates DNA damage response by triggering excess replicative stress. Transcriptomic classification of cancer cell lines based on MET expression showed that response to the PARP inhibitor (PARPi) olaparib is poorer in MET overexpressing cell lines. Accordingly, a high MET expressing lung carcinoma cell line was sensitized to PARPi by MET TK inhibition. This was not linked solely to MET overexpression: other MET overexpressing cell lines were biochemically but not functionally responsive to combined inhibition. Moreover, exogenously induced MET overexpression was unable to induce resistance to PARPi. The MET overexpressi

SUBMITTER: D'Ambrosio C 

PROVIDER: S-EPMC9146142 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature