PAK6过表达与前列腺癌进程相关，代谢重编程在前列腺癌进程中具有重要意义，但PAK6过表达在前列腺癌代谢重编程中的作用及机制尚不清楚。本项目前期筛选出PAK6新的互作蛋白-ANT2。已初步证实在葡萄糖/谷氨酰胺缺失时，PAK6与ANT2表达均下调，且过表达PAK6磷酸化并上调ANT2蛋白表达，促进ANT2乙酰化。此外，PAK6可能通过蛋白酶体途径下调SIRT4表达，进一步上调ANT2蛋白表达。本课题旨在进一步确定PAK6-ANT2信号通路在前列腺癌代谢重编程中的重要生物学功能，包括对细胞线粒体能量代谢、活性氧自由基释放、细胞凋亡及小鼠体内成瘤及转移的影响；寻找PAK6上调ANT2的分子机制，包括PAK6下调SIRT4的分子机制、PAK6介导ANT2的磷酸化与乙酰化相互调节；阐明PAK6与ANT2相互作用与前列腺癌进程与预后的关系。通过上述研究，为临床前列腺癌治疗提供新的分子靶标

PAK6 overexpression is associated with the progression of prostate cancer. Metabolic reprogramming is important in the progression of prostate cancer, but the role and mechanism of PAK6 overexpression in the metabolic reprogramming of prostate cancer is unclear. In this project, we have identified PAK6 new interactive protein -ANT2(adenine nucleotide translocase-2). It has been confirmed that both PAK6 and ANT2 expression are downregulated and ectopic expression of PAK6 phosphorylates ANT2 and promotes its acetylation following depreivation of glucose/glutamine. In addition, PAK6 may down-regulate the expression of SIRT4 by proteasome pathway and further up-regulate ANT2 protein expression. The aim of this project is to further determine the important biological function of PAK6-ANT2 signaling pathways in prostate cancer, including mitochondrial energy metabolism, release of reactive oxygen free radicals, apoptosis and tumor formation and metastasis in vivo; to explore the mechanism for PAK6 modulating ANT2 expression, including the molecular mechanism of PAK6 down-regulating SIRT4, the interaction of phosphorylation and acetylation of ANT2 by PAK6; to elucidate the correlation between the PAK6-ANT2 interaction and prostate cancer progression. Through the above studies, we will clarify the role of PAK6-ANT2 signaling pathway in the progression of prostate cancer, providing a new molecular target for the treatment of prostate cancer.