GSK-3alpha Promotes Oncogenic KRAS Function in Pancreatic Cancer via TAK1-TAB Stabilization and Regulation of Non-Canonical NF-kB

ABSTRACT: Mutations in KRAS occur in a variety of tumors of epithelial origin, driving the oncogenic phenotype.The NF-kB transcription factor pathway is important for oncogenic RAS to transform cells and to drive tumorigenesis in animal models. Recently TAK1, an upstream regulator of IKK which controls canonical NF-kB, was shown to be important for chemoresistance in pancreatic cancer and for regulating KRAS+ colorectal cancer cell growth and survival. Here we show that GSK-3alpha is upregulated by KRAS leading to interaction with TAK1 to stabilize the TAK1/TAB complex to promote IKK activity. Additionally, GSK-3alpha is required for promoting critical non-canonical NF-kB signaling in pancreatic cancer cells. Pharmacologic inhibition of GSK-3 suppresses growth of human pancreatic tumor explants, con

ORGANISM(S): Homo sapiens

SUBMITTER: Baldwin Albert 

PROVIDER: S-ECPF-GEOD-42559 | biostudies-other |

REPOSITORIES: biostudies-other