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.
Bode
Ann M
AM
The Hormel Institute, University of Minnesota, Austin, Minnesota, USA.
Cho
Yong-Yeon
YY
Zheng
Duo
D
Zhu
Feng
F
Ericson
Marna E
ME
Ma
Wei-Ya
WY
Yao
Ke
K
Dong
Zigang
Z
D000818:Animals; D002273:Carcinogens; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation; D066246:ErbB Receptors / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D017434:Protein Structure, Tertiary; D050721:Proto-Oncogene Proteins c-cbl / Q000378:metabolism; D012878:Skin Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D050916:TRPV Cation Channels / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate; D025801:Ubiquitin / Q000378:metabolism
D002273:Carcinogens; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D025801:Ubiquitin; D050721:Proto-Oncogene Proteins c-cbl; D066246:ErbB Receptors; C493849:Cbl protein, mouse; D013755:Tetradecanoylphorbol Acetate