RETRACTED ARTICLE: cGMP-phosphodiesterase 6, transducin and Wnt5a/Frizzled-2-signaling control cGMP and Ca2+ homeostasis in melanoma cells
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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.
KeywordscGMP-phosphodiesterase 6 Transducin Cancer-retina antigens Wnt Frizzled Melanoma
Intracellular calcium concentration
cGMP-dependent protein kinase
We are grateful to Mrs. A. Heinzelmann for her excellent technical assistance and Dr. M. Rogers for the English correction. This work was supported by the Intramural Program of DKFZ to A.V.B., and by the Russian Foundation for Basic Research (09-04-00395-a) and Hanse Wissenschaftskolleg, Germany to P.P.P.
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