DLC1 negatively regulates angiogenesis in a paracrine fashion.

ABSTRACT: The Rho GTPase-activating protein DLC1 is a tumor suppressor that is often deleted in liver cancer and downregulated in other cancers. DLC1 regulates the actin cytoskeleton, cell shape, adhesion, migration, and proliferation through its Rho GTPase-activating protein activity and focal adhesion localization. In this study, we silenced DLC1 in nonmalignant prostate epithelial cells to explore its tumor suppression functions. Small hairpin RNA-mediated silencing of DLC1 was insufficient to promote more aggressive phenotypes associated with tumor cell growth. In contrast, DLC1 silencing promoted pro-angiogenic responses through vascular endothelial growth factor (VEGF) upregulation, accompanied by the accumulation of hypoxia-inducible factor 1α and its nuclear localization. Notably, modulation

SUBMITTER: Shih YP 

PROVIDER: S-EPMC2970702 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature