DLC‐1:a Rho GTPase‐activating protein and tumour suppressor

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Abstract
Introduction Expression of DLC family proteins Features of DLC family protein domains Biological functions of DLC‐1 Genetic analysis of DLC‐1 function The DLC family proteins in cancer Conclusions and future directions The deleted in liver cancer 1 (DLC‐1) gene encodes a GTPase activating protein that acts as a negative regulator of the Rho family of small GTPases. Rho proteins transduce signals that influence cell morphology and physiology, and their aberrant up‐regulation is a key factor in the neoplastic process, including metastasis. Since its discovery, compelling evidence has accumulated that demonstrates a role for DLC‐1 as a bona fide tumour suppressor gene in different types of human cancer. Loss of DLC‐1 expression mediated by genetic and epigenetic mechanisms has been associated with the development of many human cancers, and restoration of DLC‐1 expression inhibited the growth of tumour cells in vivo and in vitro. Two closely related genes, DLC‐2 and DLC‐3, may also be tumour suppressors. This review presents the current status of progress in understanding the biological functions of DLC‐1 and its relatives and their roles in neoplasia.