肺癌是我国发病率和死亡率均居第一的恶性肿瘤。我们前期研究首次发现：肺癌组织中FAM13C表达水平与患者预后呈正相关；提高FAM13C表达能抑制肺癌细胞增殖、迁移、侵袭及裸鼠皮下移植瘤生长；FAM13C能显著抑制整合素介导的促癌蛋白激酶Src的活化、促进血管生成抑制因子TSP-1表达并抑制肿瘤血管生成；而缺失FAM13C近C端的突变体则失去了该效应。因此，我们推测：FAM13C是一个抑制肺癌的重要基因；FAM13C通过调控肿瘤微环境、阻遏整合素及Src等信号通路、抑制肿瘤血管生成等抑制肺癌发病。本项目拟通过临床标本、小鼠肺癌发癌和转移模型、细胞培养模型及单细胞测序等体内外实验，系统深入研究，明确FAM13C抑制肺癌的功能域及其分子作用机理，探明其调控肺癌肿瘤微环境的功能，阐明FAM13C抑制肺癌发生、进展及转移的功能及机制。研究结果将为肺癌防治提供新思路和新靶点，有重要的科学意义和转化潜力。

Lung cancer is the leading malignancy with the highest incidence and mortality in China. It is important to elucidate new tumor suppressing mechanisms for lung cancer prevention and therapy. Our preliminary studies for the first time found that the expression level of FAM13C in lung cancer tissues was positively correlated to patient survival. Ectopic FAM13C expression inhibited lung cancer cell migration and invasion in vitro and tumor growth in a xenograft mouse tumor model. FAM13C significantly inhibited the activation of integrin-mediated oncogenic kinase Src and its downstream signaling pathways related to cancer cell proliferation, invasion and metastasis, and angiogenesis. Therefore, we hypothesize that FAM13C is a potential tumor suppressor gene in lung cancer that functions through suppressing the integrin/Src signaling and angiogenesis pathways and modulating tumor microenvironment. This application will combine studies with clinical lung cancer specimens, mouse lung carcinogenesis and metastasis models and in vitro cell culture, and single cell RNA sequencing technology to systematically investigate the role and mechanism of FAM13C in suppressing lung cancer initiation, progression and metastasis. The outcome of this study will provide new insights of lung carcinogenesis mechanisms and may identify new targets for lung cancer prevention and therapy, which is significant for clinical translation.