Guanylyl Cyclase-cGMP Signaling Pathway in Melanocytes: Differential Effects of Altered Gravity in Non-Metastatic and Metastatic Cells.

Guanylyl Cyclase-cGMP Signaling Pathway in Melanocytes: Differential Effects of Altered Gravity in Non-Metastatic and Metastatic Cells.

Publication date: Feb 08, 2020

Human epidermal melanocytes as melanin producing skin cells represent a crucial barrier against UV-radiation and oxidative stress. It was shown that the intracellular signaling molecule cyclic guanosine-3′,5′-monophosphate (cGMP), generated by the guanylyl cyclases (GCs), e.g., the nitric oxide (NO)-sensitive soluble GC (sGC) and the natriuretic peptide-activated particulate GC (GC-A/GC-B), plays a role in the melanocyte response to environmental stress. Importantly, cGMP is involved in NO-induced perturbation of melanocyte-extracellular matrix interactions and in addition, increased NO production during inflammation may lead to loss of melanocytes and support melanoma metastasis. Further, the NO-sensitive sGC is expressed predominantly in human melanocytes and non-metastatic melanoma cells, whereas absence of functional sGC but up-regulated expression of GC-A/GC-B and inducible NO synthase (iNOS) are detected in metastatic cells. Thus, suppression of sGC expression as well as up-regulated expression of GC-A/GC-B/iNOS appears to correlate with tumor aggressiveness. As the cGMP pathway plays important roles in melanocyte (patho)physiology, we present an overview on the differential effects of altered gravity (hypergravity/simulated microgravity) on the cGMP signaling pathway in melanocytes and melanoma cells with different metastatic potential. We believe that future experiments in real microgravity may benefit from considering cGMP signaling as a possible factor for melanocyte transformation and in medication.

Open Access PDF

Ivanova, K. and Hemmersbach, R. Guanylyl Cyclase-cGMP Signaling Pathway in Melanocytes: Differential Effects of Altered Gravity in Non-Metastatic and Metastatic Cells. 25783. 2020 Int J Mol Sci (21):3.

Concepts Keywords
CGMP Melanocyte
Differential Hemoproteins
Environmental Stress Melanoma
Epidermal Guanylate cyclase
Extracellular Matrix Nucleotides
Gravity Branches of biology
Guanosine Radiation
Inflammation Non metastatic melanoma
INOS Tumor
Intracellular Metastasis
Melanin Guanosine monophosphate
Melanocyte Rod cell
Melanocytes Radiation
Melanoma
Metastasis
Metastatic
Microgravity
Nitric Oxide
Oxidative Stress
Particulate
Pathophysiology
Perturbation
Sci
Signaling Molecule
Tumor
UV Radiation

Semantics

Type Source Name
disease MESH oxidative stress
drug DRUGBANK Nitric Oxide
disease MESH inflammation
disease MESH melanoma
pathway KEGG Melanoma
disease MESH metastasis
disease MESH tumor

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