Journal
CANCER CELL
Volume 19, Issue 1, Pages 45-57Publisher
CELL PRESS
DOI: 10.1016/j.ccr.2010.10.029
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Funding
- Cancer Research UK [C107/A10433]
- Institute of Cancer Research
- Harry J Lloyd Charitable Trust
- FEBS (Federation of European Biochemical Societies)
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We show that in melanoma cells oncogenic BRAF, acting through MEK and the transcription factor BRN2, downregulates the cGMP-specific phosphodiesterase PDE5A. Although PDE5A downregulation causes a small decrease in proliferation, its major impact is to stimulate a dramatic increase in melanoma cell invasion. This is because PDE5A downregulation leads to an increase in cGMP, which induces an increase in cytosolic Ca2+, stimulating increased contractility and inducing invasion. PDE5A downregulation also this leads to an increase in short-term and long-term colonization of the lungs by melanoma cells. We do not observe this pathway in NRAS mutant melanoma or BRAF mutant colorectal cells. Thus, we show that in melanoma cells oncogenic BRAF induces invasion through downregulation of PDE5A.
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