Transient receptor potential type vanilloid 1 suppresses skin carcinogenesis

Cancer Res. 2009 Feb 1;69(3):905-13. doi: 10.1158/0008-5472.CAN-08-3263. Epub 2009 Jan 20.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Carcinogens
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology
  • Down-Regulation
  • ErbB Receptors / metabolism
  • Lysosomes / metabolism
  • Mice
  • Mice, Knockout
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins c-cbl / metabolism
  • Skin Neoplasms / chemically induced
  • Skin Neoplasms / genetics
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / pathology
  • TRPV Cation Channels / deficiency
  • TRPV Cation Channels / genetics
  • TRPV Cation Channels / metabolism*
  • Tetradecanoylphorbol Acetate
  • Ubiquitin / metabolism


  • Carcinogens
  • TRPV Cation Channels
  • TRPV1 protein, mouse
  • Ubiquitin
  • Proto-Oncogene Proteins c-cbl
  • ErbB Receptors
  • Cbl protein, mouse
  • Tetradecanoylphorbol Acetate