盐诱导激酶SIK2促进线粒体分裂及卵巢癌细胞糖代谢重编程的作用机制研究

糖代谢重编程在肿瘤发生进展中扮演关键角色，其调控机制一直是肿瘤代谢领域的热点问题。我们前期研究发现，作为AMPK家族成员之一的SIK2在卵巢癌细胞脂代谢与转移过程中发挥重要调控作用，然而其在卵巢癌糖代谢重编程中的作用却尚未得到系统研究。线粒体是细胞代谢调控的核心，分裂融合介导的形态改变是其代谢功能调控的重要方式，但目前，SIK2是否会通过调控线粒体分裂融合参与卵巢癌细胞线粒体代谢却尚不清楚。预实验发现：下调SIK2表达可抑制卵巢癌细胞的葡萄糖摄取及乳酸产生，并可使线粒体显著变长，提示SIK2调控卵巢癌细胞的糖酵解与线粒体分裂融合。本项目拟从分子、细胞、动物及临床组织样本四个层次，全面分析SIK2在卵巢癌细胞糖代谢重编程中的调控作用，并将首次从线粒体分裂融合动态平衡的新视角对其调控的分子机制进行深入探讨。本项目的开展可进一步加深对卵巢癌发病分子机理的认识，同时也将为其治疗提供新的潜在靶点

Cancer cells exhibit aberrant glucose metabolism, which plays important roles in tumor development and progression. The molecular mechanisms underlying glucose metabolism reprogramming of cancer cells has become a very hot field in cancer rearch.SIK2 belongs to the family of AMPK. Our previous study has shown that SIK2 is involved in the regulation of lipid metabolism and metastasis in ovarian cancer (OC)cells.However, the role of SIK2 in glucose metabolism in OC cells remains elusive. Our preliminary study showed that knockdown of SIK2 significantly suppressed glucose uptake and lactate production in OC cells, while induced the elongation of mitochondrial, indicating that SIK2 is involved in the regulation of glycolsis and mitochondrial fission and fusion. This project aims to systematically investigate the role of SIK2 in the regulation of glucose metabolism reprogramming at molecular, cellular, animal and clinical tissue sample levels, as well as to explore its underlying mechanisms from the perspective ofimbalanced mitochondrial fission and fusion. This project will not only further deepen our understanding of the molecular pathogenesis of ovarian cancer, but also provide new potentialtherapeutic targets for treatment of this malignance.