RHOA^L57V drives the development of diffuse gastric cancer through IGF1R-PAK1-YAP1 signaling.

ABSTRACT: Cancer-associated mutations in the guanosine triphosphatase (GTPase) RHOA are found at different locations from the mutational hotspots in the structurally and biochemically related RAS. Tyr⁴²-to-Cys (Y42C) and Leu⁵⁷-to-Val (L57V) substitutions are the two most prevalent RHOA mutations in diffuse gastric cancer (DGC). RHOA^Y42C exhibits a gain-of-function phenotype and is an oncogenic driver in DGC. Here, we determined how RHOA^L57V promotes DGC growth. In mouse gastric organoids with deletion of Cdh1, which encodes the cell adhesion protein E-cadherin, the expression of RHOA^L57V, but not of wild-type RHOA, induced an abnormal morphology similar to that of patient-derived DGC organoids. RHOA^L57V also exhibited a gain-of

SUBMITTER: Schaefer A 

PROVIDER: S-EPMC10791543 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature