LunX，肺特异X蛋白，正常肺不表达，癌变以后高表达，通过活化JNK和Erk信号通路促进肺癌生长和转移；临床资料显示肺脏慢性炎症疾病患者是肺癌高发人群，其LunX也呈上调状态；那么LunX是否促进肺脏慢性炎症疾病以致肺癌发生尚不清楚。初步结果显示LunX促进炎性因子IL-6、IL-1β等表达。本项目利用K-Ras-G12D自发肺癌小鼠模型、Lewis肺癌移植瘤模型和LunX转基因小鼠模型探讨LunX在肺脏早期炎症和后期肿瘤发生过程中的功能机制，具体内容包括：1.LunX作用于14-3-3蛋白促进生长相关酪氨酸激酶受体的持续活化，进而上调IL-1β、IL-6等炎性因子；2. LunX相关的炎性因子促进肺上皮细胞快速增殖、炎症细胞浸润、ROS等氧化物释放导致肿瘤发生；3. 研制抗LunX抗体抑制慢性炎症持续和肿瘤发生发展。此研究为慢性炎症与肺癌发生及治疗提供了理论依据和临床指导。

LunX(lung-specific X) is overexpressed in primary tumors of NSCLC patients but is rarely detected in benign lung disease; furthermore, high LunX protein levels are associated with poor prognosis. LunX binds to 14-3-3 proteins and thereby contributes to the activation of pathways downstream of 14-3-3, such as the Erk1/2 and JNK pathways. As a result, LunX promotes tumor growth and metastasis.The clinical data showed that patients with chronic inflammatory lung disease, such as chronic obstructive pulmonary disease, cystic fibrosis, are also up-regulated expression of LunX and more susceptible to lung cancer. Therefore, it is a worthy subject to explore: LunX promotes lung tumorigenesis by chronic inflammation. The preliminary results showed that increased expression of LunX promotes inflammatory response and cytokine secretion, such as IL-1β and IL-6. In this subject, basing on spontaneous and graft lung cancer mice modes and LunX transgenic mice, we want to investigate the mechanism of LunX contributing to tumorigenesis by causing inflammatory reaction. The research contents are as follows: (1) LunX binds to 14-3-3 proteins and thereby induces the activation of growth related tyrosine kinase receptor, such as the Erbb2, Met and etc. As a result, LunX increases inflammatory factor expression, such as the IL-1β, IL-6, CCL2 and etc. (2) LunX-induced inflammatory factors, promote tumorigenesis by epithelial cell proliferation, inflammatory cell infiltration, ROS oxide release, etc. (3) To inhibit the progression of LunX-induced inflammation and cancerization, we develop humanized anti-LunX antibodies. This study contributes to the discovery of the pathogenesis and the direction of clinical therapy in patients of lung cancer, and anti-LunX antibody is a potential therapeutic target in lung cancer.