DLC1

DLC1, short for Deleted in Liver Cancer 1, is a human tumor suppressor gene located on chromosome 8p22. It encodes a large cytosolic protein that functions as a Rho GTPase-activating protein (RhoGAP). The DLC1 protein comprises an N-terminal region, a central RhoGAP domain, a linker region that mediates interactions with focal-adhesion proteins, and a C-terminal START lipid-binding domain. Through its RhoGAP activity, DLC1 accelerates the GTP hydrolysis of Rho family GTPases, particularly RhoA, leading to decreased actin stress fibers and focal adhesions and thereby reduced cell migration and proliferation.

DLC1 localizes to focal adhesions by binding to tensin family proteins; this localization is essential for its tumor-suppressive function. Loss or silencing of DLC1 through deletions, mutations, or promoter methylation is a common event in hepatocellular carcinoma and occurs in various other cancers, contributing to increased motility, invasion, and growth.

DLC1 is regulated by phosphorylation and protein interactions; Src-family kinases can phosphorylate DLC1, modulating its activity and localization. The START domain is thought to influence lipid binding and possibly regulate its activity, adding a layer of control over the RhoGAP function.

Clinical significance and research focus on DLC1 center on its role as a tumor suppressor and its potential as a prognostic indicator. Restoring DLC1 expression or function in cancer models often inhibits tumor growth and metastasis, and ongoing studies aim to clarify its regulatory networks and therapeutic implications.