胶质瘤是最常见的中枢神经系统原发肿瘤之一，目前治疗效果非常有限，尤其是高级别胶质瘤，5年生存率低于5%，而这主要是由于胶质瘤复发率高和放化疗抵抗。研究表明，肿瘤干细胞干性维持是肿瘤复发和治疗抵抗的重要原因之一。目前认为自噬可能参与维持肿瘤干细胞干性。我们前期实验发现抑制高级别胶质瘤自噬水平可以抑制胶质瘤体内复发、降低胶质瘤细胞的放射抵抗性。同时发现中期因子MDK可能参与了胶质瘤的自噬和干性调节。在此基础上，我们提出科学问题：MDK诱导细胞自噬，通过代谢重编程，维持胶质瘤干细胞干性，进而导致胶质瘤复发和放疗抵抗。本研究将在体内外水平，深入研究自噬调节新分子MDK诱导自噬的信号通路，并进一步阐明自噬重编程代谢维持肿瘤干细胞干性的关键分子，进而导致胶质瘤复发和放疗抵抗的具体机制。通过本研究，将为胶质瘤复发和放疗抵抗提供新的研究证据和治疗靶点。

Glioma is an extremely common primary tumor of the central nervous system with very poor therapeutic effects, especially for high-grade gliomas. The 5-year survival of glioblastoma multiforme is lower than 5%, which is mainly due to the high recurrence and resistance to chemoradiotherapy. Numerous studies showed that the stemness of cancer stem cells is an significant cause for tumor relapse and radiation resistance. Some evidence indicate that autophagy may involve in maintaining stemness of cancer stem cells. In our research，high-grade glioma was found a reduced recurrence in nude mice model and a decrease in radiation resistance in human glioma cell lines when treating with autophagic inhibitors. At meantime, we also found that MDK may regulate autophagy and further promote the maintenance of stemness of cancer stem cell. Based on these data, we hypothesize that MDK-induced autophagy contributes to stemness maintenance of cancer stem cell through cell metabolic reprogramming and involves in glioma relapse and radiation resistance. In this study, we will explore the specific signaling pathway in which MDK regulates autopahgy and reprograms cell metabolism in vitro and in vivo and verify the role of cell metabolism in stemness maintenance. And our work will definitely provide new evidence and therapeutic targets for glioma treatment.