Loss of the obscurin-RhoGEF downregulates RhoA signaling and increases microtentacle formation and attachment of breast epithelial cells.

ABSTRACT: Obscurins are RhoGEF-containing proteins whose downregulation has been implicated in the development and progression of breast cancer. Herein, we aim to elucidate the mechanism for increased motility of obscurin-deficient cells. We show that shRNA-mediated obscurin downregulation in MCF10A cells leads to >50% reduction in RhoA activity relative to scramble control (shCtrl), as well as decreased phosphorylation of RhoA effectors, including myosin light chain phosphatase, myosin light chain, lim kinase, and cofilin, in both attached and suspended cells. These alterations result in decreased actomyosin contractility, allowing suspended cells to escape detachment-induced apoptosis. Moreover, ~40% of shObsc-expressing cells, but only ~10% of shCtrl-expressing cells, extend microtentacles, tubul

SUBMITTER: Perry NA 

PROVIDER: S-EPMC4226704 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature