In this issue of Cancer Cell, Arozarena et al. describe that the oncogenic BRAF Va1600Glu mutant, which occurs in about half of melanomas, downregulates the cGMP-hydrolysing phosphodiesterase PDE5A in melanoma cells through the ERK-MAPK cascade coupled to the POU-domain transcription factor BRN2, thereby increasing intracellular cGMP levels and promoting invasiveness.
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