Hic-5 regulates fibrillar adhesion formation to control tumor extracellular matrix remodeling through interaction with tensin1.

ABSTRACT: The linearization of the stromal extracellular matrix (ECM) by cancer-associated fibroblasts (CAFs) facilitates tumor cell growth and metastasis. However, the mechanism by which the ECM is remodeled is not fully understood. Hic-5 (TGFβ1i1), a focal adhesion scaffold protein, has previously been reported to be crucial for stromal ECM deposition and remodeling in vivo. Herein we show that CAFs lacking Hic-5 exhibit a significant reduction in the ability to form fibrillar adhesions, a specialized form of focal adhesion that promote fibronectin fibrillogenesis. Hic-5 was found to promote fibrillar adhesion formation through a newly characterized interaction with tensin1. Furthermore, Src-dependent phosphorylation of Hic-5 facilitated the interaction with tensin1 to prevent β1 integrin internal

SUBMITTER: Goreczny GJ 

PROVIDER: S-EPMC5876083 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature