An oncogenic KRAS transcription program activates the RHOGEF ARHGEF2 to mediate transformed phenotypes in pancreatic cancer.

ABSTRACT: Activating mutations of KRAS are nearly ubiquitous in pancreatic adenocarcinomas occurring in greater than 90% of cases. Cellular transformation by oncogenic RAS requires the RHO guanine exchange factor ARHGEF2 (also known as GEF-H1) for tumor growth and survival. Here, we find oncogenic KRAS activates ARHGEF2 through a minimal RAS responsive promoter. We have determined the endogenous ARHGEF2 promoter is positively regulated by the transcription factors ELK1, ETS1, SP1 and SP3 and negatively regulated by the RAS responsive element binding protein (RREB1). We find that the panel of ARHGEF2-regulating transcription factors modulates RAS transformed phenotypes including cellular viability, anchorage-independent growth and invasion-migration of pancreatic cancer cells. RREB1 knockdown activat

SUBMITTER: Kent OA 

PROVIDER: S-EPMC5354848 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature