Abstract
Malignant melanoma is one of the most aggressive human neoplasms which develop from the malignant transformation of normal epithelial melanocytes and share the lineage with retinal cells. cGMP-phosphodiesterase 6 (PDE6) is one of the cancer-retina antigens newly identified in melanoma cells. Normally, PDE6 hydrolyzes the photoreceptor second messenger cGMP allowing the visual signal transduction in photoreceptor cells. cGMP also play an important signaling role in stimulating melanogenesis in human melanocytes. Here, we present evidence that PDE6 is a key enzyme regulating the cGMP metabolism in melanoma cells. Decrease in intracellular cGMP leads to calcium accumulation in melanoma cells. In these cells, cGMP-phosphodiesterase 6 can be activated by another cancer-retina antigen, transducin, through Wnt5a-Frizzled-2 cascade, which leads to a lowering of cGMP and an increase in intracellular calcium mobilization. Thus, the aberrant expression of PDE6 may control cGMP metabolism and calcium homeostasis in melanoma cells.
Publication types
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Research Support, Non-U.S. Gov't
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Retracted Publication
MeSH terms
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Calcium / metabolism*
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Cell Line, Tumor
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Cyclic GMP / metabolism*
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Cyclic Nucleotide Phosphodiesterases, Type 6 / genetics
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Cyclic Nucleotide Phosphodiesterases, Type 6 / metabolism
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Cyclic Nucleotide Phosphodiesterases, Type 6 / physiology*
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Frizzled Receptors / genetics
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Frizzled Receptors / metabolism
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Frizzled Receptors / physiology*
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Homeostasis / drug effects
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Homeostasis / genetics
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Homeostasis / physiology
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Humans
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Melanoma / genetics
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Melanoma / metabolism*
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Models, Biological
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Protein Subunits / antagonists & inhibitors
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Protein Subunits / genetics
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Protein Subunits / metabolism
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins / physiology*
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RNA, Small Interfering / pharmacology
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Receptors, G-Protein-Coupled / genetics
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Receptors, G-Protein-Coupled / metabolism
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Receptors, G-Protein-Coupled / physiology*
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Signal Transduction / drug effects
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Signal Transduction / genetics
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Signal Transduction / physiology
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Skin Neoplasms / genetics
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Skin Neoplasms / metabolism*
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Transducin / genetics
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Transducin / metabolism
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Transducin / physiology*
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Wnt Proteins / genetics
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Wnt Proteins / metabolism
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Wnt Proteins / physiology*
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Wnt-5a Protein
Substances
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FZD2 protein, human
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Frizzled Receptors
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Protein Subunits
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Proto-Oncogene Proteins
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RNA, Small Interfering
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Receptors, G-Protein-Coupled
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WNT5A protein, human
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Wnt Proteins
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Wnt-5a Protein
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Cyclic Nucleotide Phosphodiesterases, Type 6
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Transducin
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Cyclic GMP
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Calcium