Sildenafil Potentiates a cGMP-Dependent Pathway to Promote Melanoma Growth | Zendy

Sandeep Dhayade | Zendy; Susanne Kaesler | Zendy; Tobias Sinnberg | Zendy; Hyazinth Dobrowinski | Zendy; Stefanie Peters | Zendy; Ulrike Naumann | Zendy; He Liu | Zendy; Robert E. Hunger | Zendy; Martin Thunemann | Zendy; Tilo Biedermann | Zendy; Birgit Schittek | Zendy; HansUwe Simon | Zendy; Susanne Feil | Zendy; Robert Feil | Zendy

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Sildenafil Potentiates a cGMP-Dependent Pathway to Promote Melanoma Growth

Author(s) -

Sandeep Dhayade,

Susanne Kaesler,

Tobias Sinnberg,

Hyazinth Dobrowinski,

Stefanie Peters,

Ulrike Naumann,

He Liu,

Robert E. Hunger,

Martin Thunemann,

Tilo Biedermann,

Birgit Schittek,

HansUwe Simon,

Susanne Feil,

Robert Feil

Publication year - 2016

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2016.02.028

Subject(s) - sildenafil , melanoma , phosphodiesterase , intracellular , pde10a , camp dependent pathway , cgmp specific phosphodiesterase type 5 , signal transduction , protein kinase a , cancer research , mapk/erk pathway , phosphodiesterase 3 , chemistry , microbiology and biotechnology , pharmacology , kinase , endocrinology , medicine , biology , biochemistry , enzyme

Sildenafil, an inhibitor of the cGMP-degrading phosphodiesterase 5 that is used to treat erectile dysfunction, has been linked to an increased risk of melanoma. Here, we have examined the potential connection between cGMP-dependent signaling cascades and melanoma growth. Using a combination of biochemical assays and real-time monitoring of melanoma cells, we report a cGMP-dependent growth-promoting pathway in murine and human melanoma cells. We document that C-type natriuretic peptide (CNP), a ligand of the membrane-bound guanylate cyclase B, enhances the activity of cGMP-dependent protein kinase I (cGKI) in melanoma cells by increasing the intracellular levels of cGMP. Activation of this cGMP pathway promotes melanoma cell growth and migration in a p44/42 MAPK-dependent manner. Sildenafil treatment further increases intracellular cGMP concentrations, potentiating activation of this pathway. Collectively, our data identify this cGMP-cGKI pathway as the link between sildenafil usage and increased melanoma risk.

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