ErbB1过表达、基因突变或活性异常增高，与非小细胞肺癌发生密切相关。TRPV1是一种阳离子通道，具有抑制肿瘤作用，但与非小细胞肺癌的相关性未有报道。我们发现ErbB1磷酸化TRPV1，且磷酸化位点是Y739。在非小细胞肺癌细胞中，过表达TRPV1抑制细胞增殖，促进细胞迁移；与之相比，过表达该位点磷酸化的激活突变体促进细胞增殖，抑制细胞迁移。ErbB1高活性的非小细胞肺癌中，TRPV1-Y739磷酸化水平、离子通道活性变化，及在非小细胞肺癌发生发展中的作用和分子机制不明，需深入研究。..本项目拟采用膜片钳、钙离子荧光标记研究TRPV1-Y739磷酸化对TRPV1通道门控及功能的影响；采用免疫组化、MTS、Annexin V/PI染色、Transwell、荷瘤小鼠模型等方法研究TRPV1及Y739磷酸化在非小细胞肺癌发生发展中的作用及分子机制，有望为非小细胞肺癌预防和治疗提供新靶点。

Lung cancer is the most common malignancy in terms of both incidence and mortality. Lung cancer are categorized into small cell lung cancer and non-small cell lung cancer (NSCLC). Nearly 85% of lung cancers are non-small cell lung cancer. ErbB1 is a member of epidermal growth factor receptor family, whose overexpression, mutation and activation is associated with NSCLC. The transient receptor vanilloid 1 (TRPV1) is a non-selective cation channel. It has reported that TRPV1 plays role in tumor inhibition. There is no report about the association between TRPV1 and NSCLC. We previously reported that ErbB1 interacts with TRPV1. Here, we found that ErbB1 phosphorylated TRPV1 at Y739. Furthermore, we found that overexpression of TRPV1 inhibited NSCLC cell proliferation while promoted NSCLC cell migration. Compared with TRPV1, overexpression of TRPV1-Y739E which is the phosphorylation constitutively active mutant promoted NSCLC cell proliferation while inhibited NSCLC cell migration. However, further studies are required to investigate the role of TRPV1 and TRPV1-Y739 phosphorylation in tumorigenesis and development in NSCLC with high activity of ErbB1.. In this study, we will use patch clamp and intracellular calcium fluorescence imaging to study the effect of TRPV1-Y739 phosphorylation on TRPV1 channel activity. A series of approaches including immunohistochemistry, MTS assay, Annexin V and propidium iodide staining, Transwell assay, tumor xenografts and so on will be used to study the role of TRPV1 and TRPV1-Y739 phosphorylation in NSCLC tumorigenesis and development. This study will provide essential evidences to reveal the function and molecular mechanism of ErbB1/TRPV1 signaling pathway in NSCLC tumorigenesis and development. It will identify a novel potential therapeutic target for NSCLC.