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

Arozarena, Imanol, Sanchez-Laorden, B., Packer, L., Hidalgo-Carcedo, C., Hayward, R., Viros, A., Sahai, E. and Marais, R. (2011) Oncogenic BRAF induces melanoma cell invasion by downregulating the cGMP-specific phosphodiesterase PDE5A. Cancer Cell, 19 (1). pp. 45-57. ISSN 1535-6108

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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 Ca(2+), 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.

Item Type: Article
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Schools: School of Applied Sciences
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Depositing User: Imanol Arozarena Arozarena
Date Deposited: 03 Mar 2015 15:40
Last Modified: 03 Mar 2015 15:40
URI: http://eprints.hud.ac.uk/id/eprint/23406

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