Oncogenic BRAF induces melanoma cell invasion by downregulating the cGMP-specific phosphodiesterase PDE5A

Imanol Arozarena, Berta Sanchez-Laorden, Leisl Packer, Cristina Hidalgo-Carcedo, Robert Hayward, Amaya Viros, Erik Sahai, Richard Marais

Research output: Contribution to journalArticlepeer-review

Abstract

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. © 2011 Elsevier Inc.
Original languageEnglish
Pages (from-to)45-57
Number of pages12
JournalCancer Cell
Volume19
Issue number1
DOIs
Publication statusPublished - 18 Jan 2011

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre

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