HMENA isoforms impact NSCLC patient outcome through fibronectin/β1 integrin axis.

ABSTRACT: We demonstrated previously that the splicing of the actin regulator, hMENA, generates two alternatively expressed isoforms, hMENA^11a and hMENAΔv6, which have opposite functions in cell invasiveness. Their mechanisms of action have remained unclear. Here we report two major findings: (i) hMENA regulates β1 integrin expression. This was shown by depleting total hMENA, which led to loss of nuclear expression of serum response factor (SRF)-coactivator myocardin-related transcription factor 1 (MRTF-A), leading to an increase in the G-actin/F-actin ratio crucial for MRTF-A localization. This in turn inhibited SRF activity and the expression of its target gene β1 integrin. (ii) hMENA^11a reduces and hMENAΔv6 increases β1 integrin activation and signaling. Moreover, exogenous

SUBMITTER: Di Modugno F 

PROVIDER: S-EPMC6193944 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature