全球癌症报告统计2018年口腔颌面部恶性肿瘤有35万新发病例和17余万死亡病例。其中，口腔鳞癌占口腔颌面部恶性肿瘤的90%，其恶性程度较高，发展快，浸润性较强，早期即可发生淋巴结转移，预后不理想。研究提示Src家族激酶在头颈部鱗癌中发挥十分重要的作用，而肿瘤抑制因子PAG1能够能特异性地感知并且负反馈调节Src家族激酶的活化。本课题组前期在急性淋巴细胞白血病的研究发现PAG1的过表达能有效抑制肿瘤细胞增殖，促进肿瘤细胞凋亡。但其机制尙不详。本项目旨在探讨PAG1在人口腔鳞癌中的表达情况，以期寻找PAG1与人口腔鳞癌组织临床病理的关系，探讨PAG1如何调控口腔鳞癌细胞的增殖，同时加入CSK抑制剂ASN2324598在体内外验证PAG1是否通过招募CSK负反馈调节Src家族激酶的活性。本项目将为口腔恶性肿瘤的诊断和基因治疗提供新的研究方向和理论依据。

The global cancer report counted 350,000 new cases of oral and maxillofacial malignancies and more than 170,000 deaths in 2018. Among them, oral squamous cell carcinoma accounts for 90% of oral and maxillofacial malignancies, with high degree of malignancy, rapid development and strong infiltration. Lymph node metastasis can occur in the early stage, and the prognosis is not ideal. It is suggested that Src family kinases play a very important role in head and neck squamous cell carcinoma, and the tumor suppressor PAG1 can specifically sense and negatively feedback the activation of Src family kinases. In our previous study on acute lymphoblastic leukemia, we found that the overexpression of PAG1 can effectively inhibit tumor cell proliferation and promote tumor cell apoptosis. But its mechanism is unclear. This project aims to investigate the expression of PAG1 in human oral squamous cell carcinoma, in order to find the relationship between PAG1 and the clinicopathology of human oral squamous cell carcinoma, to explore how PAG1 regulates the proliferation of oral squamous cell carcinoma, and to verify whether PAG1 regulates the Src family kinase activity by recruiting CSK inhibitor ASN2324598 in vitro and in vivo. This project will provide a new research direction and theoretical basis for the diagnosis and gene therapy of oral malignant tumors.