RETRACTED ARTICLE: cGMP-phosphodiesterase 6, transducin and Wnt5a/Frizzled-2-signaling control cGMP and Ca2+ homeostasis in melanoma cells

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.

Frizzled2 signaling regulates growth of high-risk neuroblastomas by interfering with β-catenin-dependent and β-catenin-independent signaling pathways

“…The binding of Wnt5a to FZD2 activates the Wnt/Ca 2+ pathway in melanoma cell lines [23]. Moreover, Wnt5a/FZD2 signaling has been shown to control cellular migration and invasion in colon cancer [21].…”

A review of 1α,25(OH)2D3 dependent Pdia3 receptor complex components in Wnt5a non-canonical pathway signaling

“…Wnt5a rapidly activates intracellular release of calcium from the endoplasmic reticulum required for PLC, PKC, CaMKII, and calcineurin activation [23][24][25][26][27]. Additionally, binding of Wnt5a to its receptor complex can activate the planar cell polarity pathway, which works via RhoA, Rasrelated C3 botulinum toxin substrate (Rac), and c-Jun N-terminal kinase (JNK)-dependent signaling pathways [26].…”

MiRNAs are Unlikely to be Involved in Retinoid Receptor Gene Regulation in Pancreatic Cancer Cells

“…Total RNA from cells was isolated using RNeasy Mini Kit following the manufacturer's instruction and described elsewhere [26]. RNA was quantified using a GeneQuant pro spectrophotometer (Eppendorf, Hamburg, Germany).…”

“…Western blotting was performed as described elsewhere [26]. Briefly, cells grown in a 24 well-plate were washed with cold phosphate-buffered saline (PBS buffer) three times and lysed in RIPA extraction buffer (150 mM sodium chloride, 1% NP-40 or Triton X-100, 0.5% sodium deoxycholate, 0.1% SDS (sodium dodecyl sulfate) and 50mM Tris at pH 8.0) on ice for 15 min.…”