PKCα Mediates mTORC1 Activation in Non-Small Cell Lung Carcinoma Cells with EGFR Deletion Mutation

Constitutively active epidermal growth factor receptor (EGFR) mutations play critical roles in the development and progression of non-small cell lung cancer (NSCLC). Patients with EGFR mutations are initially sensitive to EGFR-tyrosine kinase inhibitors; however, they eventually develop drug resistance. Therefore, thorough understanding of mutant EGFR signaling is crucial in order to avoid such resistance and develop novel control therapeutic strategies. In the present study, we observed high PKCα expression in lung adenocarcinomas and in NSCLC cells with EGFR exon 19 deletion mutation. Next, we examined the role of the highly expressed PKCα in the signaling pathways downstream of mutant EGFR. Our results demonstrated that targeting PKCα either by pharmacological inhibition or downregulation impaired mTORC1 signaling, decreased proliferation, and induced caspase-3 dependent apoptosis in cells with EGFR mutation. Moreover, PKCα gain of function was sufficient to induce proliferation of cells with wild-type...