Oncogenic BRAF induces melanoma cell invasion by downregulating the cGMP-specific phosphodiesterase PDE5A
Arozarena, Imanol, Sanchez-Laorden, Berta, Packer, Leisl M., Hidalgo-Carcedo, Cristina, Hayward, Robert, Viros, Amaya, Sahai, Erik, & Marais, Richard (2011) Oncogenic BRAF induces melanoma cell invasion by downregulating the cGMP-specific phosphodiesterase PDE5A. Cancer Cell, 19(1), pp. 45-57.
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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|Item Type:||Journal Article|
|Keywords:||B Raf kinase; calcium ion; phosphodiesterase 5A; phosphodiesterase V; unclassified drug; article; calcium cell level; cancer invasion; cell proliferation; controlled study; down regulation; enzyme regulation; human; human cell; melanoma cell; oncogene N r|
|Subjects:||Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > MEDICAL BIOCHEMISTRY AND METABOLOMICS (110100)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200) > Cancer Therapy (excl. Chemotherapy and Radiation Therapy) (111204)
|Divisions:||Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
|Deposited On:||23 Sep 2014 23:26|
|Last Modified:||24 Sep 2014 22:17|
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