EGFR基因突变、过量表达或活性异常增高，与肿瘤发生密切相关。TRPV1是一种阳离子通道，研究显示具有肿瘤抑制作用，但作用机制不明。我们曾首次报道TRPV1结合并调节EGFR；敲除TRPV1基因或使用拮抗剂，促进小鼠皮肤癌发生。 我们新近又发现EGFR使TRPV1磷酸化。然而，在EGFR高活性的肿瘤中，TRPV1的磷酸化水平、离子通道活性的改变、以及在肿瘤发生发展中的作用和分子机制不明，需深入研究。 本项目拟采用GST pull-down、免疫荧光染色、点突变、激酶实验、膜片钳、钙离子荧光标记、siRNA、平板集落形成、AnnexinV/PI双染法、Tunel法、Transwell小室、荷瘤小鼠模型等方法，研究EGFR对TRPV1的磷酸化作用，阐明该作用对TRPV1通道门控及通道功能的影响，探索EGFR与TRPV1通路间的串话机制，以及在肿瘤发生发展中的作用，为肿瘤预防和治疗提供新靶点。

EGFR is a member of epidermal growth factor receptor family, which is overexpressed and activated in many human epithelial cancers and is associated with tumor development. The transient receptor vanilloid 1 (TRPV1) is a non-selective cation channel.It was reported that TRPV1 inhibited tumor development, while the detailed mechanism remained unclear. We previously reported that EGFR interacted with TRPV1. The absence of TRPV1 in mice or the topical application of TRPV1 antagonist resulted in a striking increase in skin carcinogenesis mediated through a significant increase in the expression level of EGFR and the activity of its downstream signaling pathway. Here，we found that EGFR phosphorylated TRPV1 in vitro. However, further studies are required to investigate the phosphorylation level of TRPV1 and the activity of phosphorlyated TRPV1 channel as well as its role in tumor development in the tumors with high activity of EGFR. In this study, we propose to utilize different experimental methods including co-immunoprecipitation, GST pull- down, immunofluorescence, point mutation, kinase assay, patch clamp, intracellular calcium fluorescence imaging, siRNA, foci formation, Annexin V and propidium iodide staining, Tunel assay, Transwell assay, tumor xenografts and so on, to study the phosphorylation of TRPV1 by EGFR, to identify the effect on TRPV1 channel, and to investigate the relationship between EGFR and TRPV1 signaling in tumor development. Our research will present important evidences to reveal the crosstalk of EGFR and TRPV1 signaling pathway, and the molecular mechanism and the function of EGFR/TRPV1 signaling in tumor development. These might provide significant theoretical and experimental supports to the study on EGFR/TRPV1 related tumorigenesis, and develop potential targets in cancer prevention and therapy.