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Transient receptor potential type vanilloid 1 suppresses skin carcinogenesis.

Blockade of the transient receptor potential channel vanilloid subfamily 1 (TRPV1) is suggested as a therapeutic approach to pain relief. However, TRPV1 is a widely expressed protein whose function might be critical in various nonneuronal physiologic conditions. The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is overexpressed in many human epithelial cancers and is a potential target for anticancer drugs. Here, we show that TRPV1 interacts with EGFR, leading to EGFR degradation. Notably, the absence of TRPV1 in mice results in a striking increase in skin carcinogenesis. The TRPV1 is the first membrane receptor shown to have a tumor-suppressing effect associated with the down-regulation of another membrane receptor. The data suggest that, although a great deal of interest has focused on TRPV1 as a target for pain relief, the chronic blockade of this pain receptor might increase the risk for cancer development.

Pubmed ID: 19155296

Authors

  • Bode AM
  • Cho YY
  • Zheng D
  • Zhu F
  • Ericson ME
  • Ma WY
  • Yao K
  • Dong Z

Journal

Cancer research

Publication Data

February 1, 2009

Associated Grants

  • Agency: NCI NIH HHS, Id: CA007646
  • Agency: NCI NIH HHS, Id: CA027502
  • Agency: NCI NIH HHS, Id: CA088961
  • Agency: NCI NIH HHS, Id: CA111536
  • Agency: NCI NIH HHS, Id: CA120388
  • Agency: NCI NIH HHS, Id: P01 CA027502
  • Agency: NCI NIH HHS, Id: P01 CA027502-270022
  • Agency: NCI NIH HHS, Id: P01 CA088961
  • Agency: NCI NIH HHS, Id: P01 CA088961-020003
  • Agency: NCI NIH HHS, Id: R01 CA077646
  • Agency: NCI NIH HHS, Id: R01 CA077646-09
  • Agency: NCI NIH HHS, Id: R01 CA081064
  • Agency: NCI NIH HHS, Id: R01 CA081064-08
  • Agency: NCI NIH HHS, Id: R01 CA111536
  • Agency: NCI NIH HHS, Id: R01 CA111536-04
  • Agency: NCI NIH HHS, Id: R01 CA120388
  • Agency: NCI NIH HHS, Id: R01 CA120388-03
  • Agency: NCI NIH HHS, Id: R37 CA081064

Mesh Terms

  • Animals
  • Carcinogens
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic
  • Down-Regulation
  • Lysosomes
  • Mice
  • Mice, Knockout
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins c-cbl
  • Receptor, Epidermal Growth Factor
  • Skin Neoplasms
  • TRPV Cation Channels
  • Tetradecanoylphorbol Acetate
  • Ubiquitin