Antje Schaefer, Richard G Hodge, Haisheng Zhang, G Aaron Hobbs, Julien Dilly, Minh V Huynh, Craig M Goodwin, Feifei Zhang, J Nathaniel Diehl, Mariaelena Pierobon, Elisa Baldelli, Sehrish Javaid, Karson Guthrie, Naim U Rashid, Emanuel F Petricoin, Adrienne D Cox, William C Hahn, Andrew J Aguirre, Adam J Bass, Channing J Der
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). RHOAY42C exhibits a gain-of-function phenotype and is an oncogenic driver in DGC. Here, we determined how RHOAL57V promotes DGC growth. In mouse gastric organoids with deletion of Cdh1 , which encodes the cell adhesion protein E-cadherin, the expression of RHOAL57V , but not of wild-type RHOA, induced an abnormal morphology similar to that of patient-derived DGC organoids...
December 19, 2023: Science Signaling