Sildenafil Potentiates a cGMP-Dependent Pathway to Promote Melanoma Growth.
- Dhayade S Interfakultäres Institut für Biochemie, University of Tübingen, 72076 Tübingen, Germany.
- Kaesler S Department of Dermatology, University of Tübingen, 72076 Tübingen, Germany.
- Sinnberg T Department of Dermatology, University of Tübingen, 72076 Tübingen, Germany.
- Dobrowinski H Interfakultäres Institut für Biochemie, University of Tübingen, 72076 Tübingen, Germany.
- Peters S Interfakultäres Institut für Biochemie, University of Tübingen, 72076 Tübingen, Germany.
- Naumann U Hertie-Institut für klinische Hirnforschung, Abteilung Vaskuläre Neurologie, Labor für Molekulare Neuroonkologie, 72076 Tübingen, Germany.
- Liu H Institute of Pharmacology, University of Bern, 3010 Bern, Switzerland.
- Hunger RE Department of Dermatology, Inselspital, University Hospital Bern, 3010 Bern, Switzerland.
- Thunemann M Interfakultäres Institut für Biochemie, University of Tübingen, 72076 Tübingen, Germany.
- Biedermann T Department of Dermatology, University of Tübingen, 72076 Tübingen, Germany; Department of Dermatology and Allergology, Technische Universität München, 80802 Munich, Germany.
- Schittek B Department of Dermatology, University of Tübingen, 72076 Tübingen, Germany.
- Simon HU Institute of Pharmacology, University of Bern, 3010 Bern, Switzerland.
- Feil S Interfakultäres Institut für Biochemie, University of Tübingen, 72076 Tübingen, Germany.
- Feil R Interfakultäres Institut für Biochemie, University of Tübingen, 72076 Tübingen, Germany. Electronic address: robert.feil@uni-tuebingen.de.
- 2016-03-15
Published in:
- Cell reports. - 2016
Animals
Butadienes
Cell Line, Tumor
Cell Movement
Cell Proliferation
Cyclic GMP
Cyclic GMP-Dependent Protein Kinase Type I
Cyclic Nucleotide Phosphodiesterases, Type 5
Female
Humans
Melanoma
Mice
Mice, Inbred C57BL
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
Natriuretic Peptide, C-Type
Nitriles
Phosphodiesterase 5 Inhibitors
Protein Isoforms
Signal Transduction
Sildenafil Citrate
Transplantation, Homologous
English
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.
- Language
-
- English
- Open access status
- gold
- Identifiers
-
- DOI 10.1016/j.celrep.2016.02.028
- PMID 26971999
- Persistent URL
- https://folia.unifr.ch/global/documents/155299
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