Bode Ann M, Cho Yong-Yeon, Zheng Duo, Zhu Feng, Ericson Marna E, Ma Wei-Ya, Yao Ke, Dong Zigang
The Hormel Institute, University of Minnesota, Austin, Minnesota, USA.
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.
瞬时受体电位香草酸亚型1（TRPV1）通道的阻断被认为是缓解疼痛的一种治疗方法。然而，TRPV1是一种广泛表达的蛋白质，其功能在各种非神经元生理状况下可能至关重要。表皮生长因子受体（EGFR）是一种受体酪氨酸激酶，在许多人类上皮癌中过度表达，是抗癌药物的一个潜在靶点。在此，我们表明TRPV1与EGFR相互作用，导致EGFR降解。值得注意的是，小鼠中TRPV1的缺失导致皮肤癌发生显著增加。TRPV1是首个被证明具有与另一种膜受体下调相关的肿瘤抑制作用的膜受体。这些数据表明，尽管人们对将TRPV1作为缓解疼痛的靶点极为关注，但长期阻断这种疼痛受体会增加癌症发生的风险。
