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GAP-independent functions of DLC1 in metastasis

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Abstract

Metastases are responsible for most cancer-related deaths. One of the hallmarks of metastatic cells is increased motility and migration through extracellular matrixes. These processes rely on specific small GTPases, in particular those of the Rho family. Deleted in liver cancer-1 (DLC1) is a tumor suppressor that bears a RhoGAP activity. This protein is lost in most cancers, allowing malignant cells to proliferate and disseminate in a Rho-dependent manner. However, DLC1 is also a scaffold protein involved in alternative pathways leading to tumor and metastasis suppressor activities. Recently, substantial information has been gathered on these mechanisms and this review is aiming at describing the potential and known alternative GAP-independent mechanisms allowing DLC1 to impair migration, invasion, and metastasis formation.

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Acknowledgments

We thank Lluis Fajas and Mathieu Heulot for valuable comments on this review. We apologize to colleagues whose work was not highlighted owing to space limitations. C.W. is supported by grants from the Swiss National Science Foundation (no. 31003A_141242/1) and the Swiss Cancer League (no. KFS-02543-02-2010).

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  1. Department of Physiology, University of Lausanne, Bugnon 7, 1005, Lausanne, Switzerland

    David Barras & Christian Widmann

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Correspondence to Christian Widmann.

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Barras, D., Widmann, C. GAP-independent functions of DLC1 in metastasis. Cancer Metastasis Rev 33, 87–100 (2014). https://doi.org/10.1007/s10555-013-9458-0

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