Synthetic Lethal Interaction Between Oncogenic KRAS Dependency and Suppression of STK33 in Human Cancer Cells

ABSTRACT: Many human oncogenes are challenging therapeutic targets. An alternative to direct targeting of oncogenes is to perform â??synthetic lethalityâ?? screens for genes that are essential only in the context of specific cancer-causing mutations. We used high-throughput RNA interference (RNAi) to identify synthetic lethal interactions in cancer cells harboring mutant KRAS, the most commonly mutated human oncogene. We find that cells that are dependent on mutant KRAS exhibit sensitivity to suppression of the serine/threonine kinase STK33 irrespective of tissue origin, whereas STK33 is not required by KRAS-independent cells. STK33 promotes cancer cell viability in a kinase activity-dependent manner by regulating the suppression of mitochondrial apoptosis mediated through S6K1-induced inactivation

ORGANISM(S): Homo sapiens

SUBMITTER: Lars Bullinger 

PROVIDER: E-GEOD-15151 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress