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.
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- [Ca2+]i :
Intracellular calcium concentration
cGMP-dependent protein kinase
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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.
The Editor-in-Chief has retracted this article  due to errors in Figure 1B, Figure 1C and Figure 4.
In Figure 1 a number of panels are replicated between experimental groups:
In Figure 1B, the MaMel 04/β-actin control for PDE6α panel replicates β-actin panel 8 in Figure 1C.
In Figure 1B, the MaMel 04/β-actin control for PDE6β panel replicates β-actin panels 1 and 2 in Figure 1C.
In Figure 1B, the MaMel 11/β-actin control for PDE6β panel replicates β-actin panels 11 and 12 in Figure 1C.
In Figure 1B, the MaMel 11/β-actin control for PDE6γ panel replicates β-actin panels 13 and 14 in Figure 1C.
In Figure 1B, the MaMel 11/PDE6α panel reproduces panels 2 and 3 in the PKGIα/β band from Figure 1 in .
In Figure 1C, the β-actin panels 1-7 reproduce panels 1-7 in the GAPDH band from Figure 1 in .
In Figure 4, the Transducin and Wnt5a bands appear to be spliced.
Alexandr V. Bazhin, Dirk Schadendorf and Stefan B. Eichmüller agree to this retraction. Vojtech Tambor and Pavel P. Philippov have not responded to any correspondence from the publisher about this retraction. Boyan Dikov could not be contacted.
1. Bazhin AV, Tambor V, Dikov B, Philippov PP, Schadendorf D, Eichmüller SB. cGMP-phosphodiesterase 6, transducin and Wnt5a/Frizzled-2-signaling control cGMP and Ca 2+ homeostasis in melanoma cells. Cellular and molecular life sciences. 2010 Mar 1;67(5):817-28.
2. Karakhanova S, Golovastova M, Philippov PP, Werner J, Bazhin AV. Interlude of cGMP and cGMP/protein kinase G type 1 in pancreatic adenocarcinoma cells. Pancreas. 2014 Jul 1;43(5):784-94. doi: 10.1097/MPA.0000000000000104
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Bazhin, A.V., Tambor, V., Dikov, B. et al. RETRACTED ARTICLE: cGMP-phosphodiesterase 6, transducin and Wnt5a/Frizzled-2-signaling control cGMP and Ca2+ homeostasis in melanoma cells. Cell. Mol. Life Sci. 67, 817–828 (2010). https://doi.org/10.1007/s00018-009-0214-0
- cGMP-phosphodiesterase 6
- Cancer-retina antigens