鼻咽癌（NPC）是源于鼻咽部黏膜上皮，对放疗敏感的恶性肿瘤。放疗抵抗是NPC治疗失败的主要原因。DNA损伤应答（DDR）与放疗抵抗密切相关。细胞骨架蛋白TAGLN在肿瘤中的作用存在争议。前期通过生信数据筛选的TAGLN与NPC放疗抵抗和DDR相关，TAGLN能被放射诱导表达和DNA-PKcs/ATM磷酸化，调控细胞周期阻滞。基于此，我们提出假设：TAGLN在NPC放疗中作为ATM/DNA-PKcs底物被磷酸化，促进P53的稳定，发挥放疗抵抗作用。本研究首先明确TAGLN与NPC临床特征的关联；其次证实TAGLN在NPC中的放疗抵抗作用；然后证明作为底物的TAGLN与DNA-PKcs/ATM相互作用并明确位点；再次，阐明TAGLN的放疗抵抗作用依赖于DNA-PKcs/ATM磷酸化；最后体内验证TAGLN在NPC放疗抵抗中的作用及机制。本研究目的是为提高NPC放疗敏感性提供策略和理论依据。

Nasopharyngeal carcinoma (NPC) is a malignant tumor that originates from the mucosal epithelium of the nasopharyngeal mucosa and is sensitive to radiotherapy.Radiotherapy resistance is the main cause of NPC treatment failure. DNA damage Response (DDR) is closely related to radiotherapy resistance. The role of cytoskeleton protein TAGLN in tumors is controversial. Our previous study showed that TAGLN is related with NPC radiotherapy resistance and DDR, and the expression of TAGLN in NPC can be induced by radiaotherapy. TAGLN could be phosphorylated by DNA-PKcs or ATM, and regelates cell cycle arrest. Based on this, we put forward the hypothesis that as ATM/DNA-PKCS substrate, TAGLN interacts with DNA-PKcs or ATM is phosphorylated by DNA-PKcs or ATM, promotes the stability of p53, and plays the role of radiotherapy resistance during NPC radiotherapy. In this study, we first identified the association between TAGLN and NPC clinical features. Secondly, the radiotherapy resistance role of TAGLN in NPC was confirmed. Then, it is proved that the TAGLN as the substrate interacts with the DN-PKCS/ATM and clarifies the phosphoraylated sites. Thirdly, it is elucidated that the radiotherapy resistance of TAGLN depends on DNA-PKCS/ATM phosphorylation. Finally, the role and mechanism of TAGLN in NPC radiotherapy resistance were verified in vivo. The purpose of this study is to provide strategy for improving the sensitivity of NPC radiotherapy.