| First Author | Kenchappa RS | Year | 2021 |
| Journal | Cell Rep | Volume | 37 |
| Issue | 8 | Pages | 110054 |
| PubMed ID | 34818553 | Mgi Jnum | J:332501 |
| Mgi Id | MGI:6881807 | Doi | 10.1016/j.celrep.2021.110054 |
| Citation | Kenchappa RS, et al. (2021) Protein kinase Ciota and SRC signaling define reciprocally related subgroups of glioblastoma with distinct therapeutic vulnerabilities. Cell Rep 37(8):110054 |
| abstractText | We report that atypical protein kinase Ciota (PKCiota) is an oncogenic driver of glioblastoma (GBM). Deletion or inhibition of PKCiota significantly impairs tumor growth and prolongs survival in murine GBM models. GBM cells expressing elevated PKCiota signaling are sensitive to PKCiota inhibitors, whereas those expressing low PKCiota signaling exhibit active SRC signaling and sensitivity to SRC inhibitors. Resistance to the PKCiota inhibitor auranofin is associated with activated SRC signaling and response to a SRC inhibitor, whereas resistance to a SRC inhibitor is associated with activated PKCiota signaling and sensitivity to auranofin. Interestingly, PKCiota- and SRC-dependent cells often co-exist in individual GBM tumors, and treatment of GBM-bearing mice with combined auranofin and SRC inhibitor prolongs survival beyond either drug alone. Thus, we identify PKCiota and SRC signaling as distinct therapeutic vulnerabilities that are directly translatable into an improved treatment for GBM. |
