BRAF-induced tumorigenesis is IKKalpha dependent but NF?B independent

ABSTRACT: Tumor cells carrying KRAS mutations activate the NF-?B pathway by different mechanisms, which contribute to the acquisition of essential cancer properties. The BRAF kinase, a downstream mediator of KRAS, is also mutated in a subset of colorectal cancers (CRC), which predicts bad prognosis and therapy resistance. However, nothing is known on whether NF-?B participates of BRAF-mediated tumorigenesis. We here found that in CRC cells, mutant BRAF does not trigger canonical or alternative NF-?B signaling but induces p45-IKK? activation. Moreover, IKK? activity is required for BRAF-induced transformation and to support BRAF-dependent transcription in CRC cells. Activation of p45-IKK? downstream of BRAF requires the TAK1 kinase, and is associated to the endosomal compartment. Inhibition of endoso

ORGANISM(S): Homo sapiens

SUBMITTER: Lara Nonell 

PROVIDER: E-GEOD-57979 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress