DGC-specific RHOA mutations maintained cancer cell survival and promoted cell migration via ROCK inactivation.

ABSTRACT: RHOA missense mutations exist specifically in diffuse type gastric cancers (DGC) and are considered one of the DGC driver genes, but it is not fully understood how RHOA mutations contribute to DGC development. Here we examined how RHOA mutations affect cancer cell survival and cell motility. We revealed that cell survival was maintained by specific mutation sites, namely G17, Y42, and L57. Because these functional mutations suppressed MLC2 phosphorylation and actin stress fiber formation, we realized they act in a dominant-negative fashion against the ROCK pathway. Through the same inactivating mechanism that maintained cell survival, RHOA mutations also increased cell migration activity. Cell survival and migration studies on CLDN18-ARHGAP (CLG) f

SUBMITTER: Nishizawa T 

PROVIDER: S-EPMC5955407 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature