ABSTRACT
Protein kinase C (PKC)É, a member of the novel PKC family, has key roles in mitogenesis and survival in normal and cancer cells. PKCÉ is frequently overexpressed in epithelial cancers, particularly in lung cancer. Using a short-hairpin RNA approach, here we established that PKCÉ is required for non-small cell lung carcinoma (NSCLC) growth in vitro as well as tumor growth when inoculated into athymic mice. Moreover, sustained delivery of a PKCÉ-selective inhibitor peptide, ÉV1-2, reduced xenograft growth in mice. Both RNA interference depletion and pharmacological inhibition of PKCÉ caused a marked elevation in the number of apoptotic cells in NSCLC tumors. PKCÉ-depleted NSCLC cells show elevated expression of pro-apoptotic proteins of the Bcl-2 family, caspase recruitment domain-containing proteins and tumor necrosis factor ligands/receptor superfamily members. Moreover, a Gene Set Enrichment Analysis revealed that a vast majority of the genes changed in PKCÉ-depleted cells were also deregulated in human NSCLC. Our results strongly suggest that PKCÉ is required for NSCLC cell survival and maintenance of NSCLC tumor growth. Therefore, PKCÉ may represent an attractive therapeutic target for NSCLC.