炎症和感染被认为是促进肺癌发生的重要原因之一。然而，其作用机理不清。在前期研究中我们发现，Gprc5a-敲除(ko)小鼠可发生肺癌，同时对炎症信号易感。最近我们发现，呼吸道常见革兰氏阴性菌非典型性流感嗜血杆菌可促进Gprc5a-ko小鼠肺癌发生。这提示Gprc5a的缺失导致了TLR4介导的炎症信号的异常性激活。我们假设，GPRC5A通过与MyD88的结合，同时调控了TLR4和IL-1R介导的NF-κB信号通路激活；Gprc5a的缺失导致这些通路的持续性激活，进而促进了肺癌的炎-癌转化进程。本课题拟从实验动物、细胞生物学、分子生物学和临床样本等层面，阐释炎症因子LPS和IL-1β促进肺癌发生发展的机理，并深入挖掘GPRC5A与TLR4/IL-1R-MyD88-NF-κB信号通路间的调控机制。本研究有助于发现GPRC5A阻碍肺癌炎-癌转化进程的分子机制，为肺癌的诊疗和防治提供理论基础。

Inflammation and infection are considered to be the major causes in promotion of lung cancer. However, the underlying mechanism is not clear. In the previous study, we showed that Gprc5a knockout (ko) mice can develop lung cancer and are susceptible to LPS induced inflammatory signals. Recently, we found that nontypeable Haemophilus influenzae (NTHi) in the respiratory tract can promote the development of lung cancer in Gprc5a-ko mice. This suggests that Gprc5a-deficiency leads to aberrant activation of TLR4-mediated inflammatory signal. We hypothesized that GPRC5A, through its interaction with MyD88, regulates TLR4- and IL-1R-mediated NF-κB signaling pathway; whereas Gprc5a deletion leads to sustained activation of inflammatory signaling pathway, thereby promoting the process of inflammation-transformation-lung tumorigenesis. In this study, we propose to explore the roles and mechanisms of LPS and IL-1β in lung tumorigenesis in multiple levels, animal model, cell biology, molecular biology and clinical samples; we will further explore the regulatory mechanism between GPRC5A and TLR4/IL-1R-MyD88-NF-κB signaling pathway. This study is to reveal the molecular mechanism of GPRC5A-mediated inhibition of inflammation-transformation-tumorigenesis in lung, which would provide the theoretical basis for the diagnosis, treatment and prevention of lung cancer.