TM9SF4是具有9个跨膜结构域和一个N端可变胞外结构域的超家族成员。目前研究发现它参与了同类相食，细胞粘附和癌细胞耐药等活动，且在黑色素瘤细胞高表达。我们已发表的数据表明TM9SF4促进细胞自噬，前期结果显示与肺正常上皮细胞相比，TM9SF4高表达于肺癌细胞，且敲低TM9SF4会抑制肺癌细胞生长并促进其凋亡，因此TM9SF4可能在肿瘤细胞的凋亡中起关键的作用，然而其在调控肿瘤细胞凋亡中的具体的角色和机理尚不清楚。本研究拟运用体内、体外模型，利用免疫印迹，免疫荧光和流式细胞术等方法，多角度验证TM9SF4调控细胞凋亡的机制。并结合内质网应激抑制剂4-PBA和caspase9的抑制剂等在细胞水平和动物水平上，解析其发挥功能效应的途径。该项目的完成不仅能揭示TM9SF4在调控肿瘤细胞凋亡的作用机制，阐明TM9SF4在成瘤发生的作用，还将为肿瘤的诊断治疗提供新的潜在标记物和实验理论依据。

TM9SF4 is a transmembrane protein belonging to the transmembrane-9 superfamily (TM9SF), which is a well-defined family of proteins characterized by a large hydrophilic N-terminal domain followed by nine transmembrane domains. It has been implicated to participate in multiple cellular processes such as tumor cannibalism, cell adhesion and drug-resistance of cancer cells and it is highly expressed in the melanoma cells. Our published data showed that TM9SF4 promotes autophagy and our recent studies showed that TM9SF4 is highly expressed in cancer cells compared to normal cells, and knockdown of TM9SF4 inhibits cancer cell proliferation and promotes apoptosis. However, the exact role and mechanism of TM9SF4 in regulating lung cancer cell apoptosis is not known. This study is focused on the mechanism by which TM9SF4 regulates cancer cell apoptosis both in vitro and in vivo, using microplate reader, immunoblot, immunostaining and flow cytometry et.al. Meanwhile, the endoplasmic reticulum stress inhibitor 4-PBA and caspase 9 inhibitor will be used to study the mechanism of TM9SF4 regulation of apoptosis. The expected results will not only reveal the mechanism of TM9SF4 regulation on tumor cell apoptosis, but also provide a new markers and experimental theoretical basis for the diagnosis and treatment of tumors.