The RhoJ-BAD signaling network: An Achilles' heel for BRAF mutant melanomas

作者：Ruiz Rolando; Jahid Sohail; Harris Melissa; Marzese Diego M; Espitia Francisco; Vasudeva Priya; Chen Chi Fen; de Feraudy Sebastien; Wu Jie; Gillen Daniel L; Krasieva Tatiana B; Tromberg Bruce J; Pavan William J; Hoon Dave S; Ganesan Anand K^*

来源：PLoS Genetics, 2017, 13(7): e1006913.

DOI：10.1371/journal.pgen.1006913

Genes and pathways that allow cells to cope with oncogene-induced stress represent selective cancer therapeutic targets that remain largely undiscovered. In this study, we identify a RhoJ signaling pathway that is a selective therapeutic target for BRAF mutant cells. RhoJ deletion in BRAF mutant melanocytes modulates the expression of the pro-apoptotic protein BAD as well as genes involved in cellular metabolism, impairing nevus formation, cellular transformation, and metastasis. Short-term treatment of nascent melanoma tumors with PAK inhibitors that block RhoJ signaling halts the growth of BRAF mutant melanoma tumors in vivo and induces apoptosis in melanoma cells in vitro via a BAD-dependent mechanism. As up to 50% of BRAF mutant human melanomas express high levels of RhoJ, these studies nominate the RhoJ-BAD signaling network as a therapeutic vulnerability for fledgling BRAF mutant human tumors.

• 出版日期2017-7
• 单位NIH