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

doi:10.1016/j.ccr.2010.10.029

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

Cancer Research UK Manchester Institute

Research output: Contribution to journal › Article › peer-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 language	English
Pages (from-to)	45-57
Number of pages	12
Journal	Cancer Cell
Volume	19
Issue number	1
DOIs	https://doi.org/10.1016/j.ccr.2010.10.029
Publication status	Published - 18 Jan 2011

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10.1016/j.ccr.2010.10.029

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title = "Oncogenic BRAF induces melanoma cell invasion by downregulating the cGMP-specific phosphodiesterase PDE5A",

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. {\textcopyright} 2011 Elsevier Inc.",

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

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T1 - Oncogenic BRAF induces melanoma cell invasion by downregulating the cGMP-specific phosphodiesterase PDE5A

AU - Arozarena, Imanol

AU - Sanchez-Laorden, Berta

AU - Packer, Leisl

AU - Hidalgo-Carcedo, Cristina

AU - Hayward, Robert

AU - Viros, Amaya

AU - Sahai, Erik

AU - Marais, Richard

N1 - C107/A10433, Cancer Research UK, United Kingdom

PY - 2011/1/18

Y1 - 2011/1/18

N2 - 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.

AB - 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.

U2 - 10.1016/j.ccr.2010.10.029

DO - 10.1016/j.ccr.2010.10.029

M3 - Article

C2 - 21215707

SN - 1878-3686

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JO - Cancer Cell

JF - Cancer Cell

IS - 1

ER -

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

Abstract

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