失巢凋亡抗性是造成肿瘤化疗耐药及复发转移的重要原因。我们前期研究发现，化疗耐药舌鳞癌细胞失巢凋亡抗性增强，细胞发生了EMT，侵袭迁移能力增强；此外，Ezrin蛋白的激活可调控舌鳞癌细胞EMT及转移；预实验发现在耐药舌鳞癌细胞中敲除Ezrin的表达可抑制FAK激活，逆转细胞失巢凋亡抗性。但是，Ezrin对耐药舌鳞癌细胞失巢凋亡抗性的调控机制尚不明确。本项目先在耐药舌鳞癌细胞中研究Ezrin与整合蛋白及FAK的关系，进一步在细胞和动物模型中研究Ezrin及相关上下游信号对舌鳞癌耐药细胞失巢凋亡抗性、EMT及侵袭转移能力的影响，在临床样本中检测磷酸化Ezrin和相关蛋白与细胞凋亡及患者化疗敏感性、预后的关系，探索Ezrin及相关上下游信号通路调控耐药舌鳞癌细胞失巢凋亡抗性的分子机制。通过本研究可进一步完善化疗耐药舌鳞癌失巢凋亡抗性的调控机制，为研制针对舌鳞癌化疗抗性及转移的靶向药物提供实验依据。

Anoikis resistance is the essential cause of tumor chemotherapy resistance, recurrence and metastasis. Our previous study demostrated that chemoresistant human tongue squamous cancer cell (TSCC) was resistant to anoikis，undergone EMT, and promoted cell invasion and migration. On the other hand, we found that activation of cytoskeletal crosslinker Ezrin regulated EGF-induced EMT and metastasis of TSCC. Our Pre-Experiment data indicated that Ezrin knockdown in chemoresistant TSCC inhibited FAK activation and anoikis resistance. However，the mechanism underlying Ezrin regulating anoikis resistance of TSCC is still unclear. The project plans to study the relation among Ezrin、FAK and integrin in chemoresistant TSCC cells. Then study the effect Ezrin signal pathway on anoikis resistance, EMT, and invasiveness and metastasis of tumor cell by using cellular and animal models. The project then plans to evaluate the relationship between Ezrin signal pathway and cell apoptosis, patient chemotherapy sentivity and prognosis. The project will identify the molecular mechanism involved in anoikis resistance of chemoresistant TSCC, and provide experimental foundations for development targeted therapy aimed for reversing TSCC chemoresistance and metastasis.