Deleted in liver cancer-1 (DLC-1): a tumor suppressor not just for liver.
Deleted in liver cancer 1 (DLC-1), as its name implied, was originally isolated as a potential tumor suppressor gene often deleted in hepatocellular carcinoma. Further studies have indicated that down-expression of DLC-1 either by genomic deletion or DNA methylation is associated with a variety of cancer types including lung, breast, prostate, kidney, colon, uterus, ovary, and stomach. Re-expression of DLC-1 in cancer cells regulates the structure of actin cytoskeleton and focal adhesions and significantly inhibits cell growth, supporting its role as a tumor suppressor. This tumor suppressive function relies on DLC-1's RhoGTPase activating protein (RhoGAP) activity and steroidogenic acute regulatory (StAR)-related lipid transfer (START) domain, as well as its focal adhesion localization, which is recruited by the Src Homology 2 (SH2) domains of tensins in a phosphotyrosine-independent fashion. Therefore, the expression and subcellular localization of DLC-1 could be a useful molecular marker for cancer prognosis, whereas DLC-1 and its downstream signaling molecules might be therapeutic targets for the treatment of cancer.
Liao
Yi-Chun
YC
Lawrence Ellison Center for Tissue Regeneration and Repair, Department of Biochemistry and Molecular Medicine, University of California, Davis, Sacramento, CA 95817, USA.
Lo
Su Hao
SH
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics; D020690:GTPase-Activating Proteins; D005786:Gene Expression Regulation; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics; D051379:Mice; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy; D017434:Protein Structure, Tertiary; D051381:Rats; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
C112352:DLC1 protein, human; D020690:GTPase-Activating Proteins; D025521:Tumor Suppressor Proteins