Oral communication, CS16 / C74

Official XXIst International Pigment Cell Conference website - 21-24 Sept 2011, Bordeaux - France | updated: September 04 2011

Synthetic Lethal RNAi-screening Uncovers a Novel Role for Rho Family GTPases in Controlling Cell Fate and Chemoresistance

Melanoma is resistant to conventional chemotherapy, immunotherapy, and molecularly-directed therapies via unknown mechanisms. In this study, we utilized a systems-level functional genomics approach to identify novel pathways that modulate melanoma chemoresponsiveness. In addition to isolating fragile nodes in the DNA repair network, this analysis identified two Rho family GTPases (RhoJ, Rnd2) as pathological suppressors of melanoma cell sensitivity to DNA damage. Mechanistic studies revealed that RhoJ supports melanoma migration and invasion, and is necessary and sufficient to drive the expression of Sox10, a central regulator of melanocyte lineage specification. Sox10 is overexpressed in melanoma and required for melanoma cell survival. These observations uncover a novel role for Rho family G-proteins in cell fate specification and implicate melanocytic lineage specification as an intrinsic chemoresistance determinant.

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