Lu Jiayi, Wang Xiaoyun, Shi Xiaodan, Jiang Junyi, Liu Lan, Liu Lu, Ren Chune, Lu Chao, Yu Zhenhai
Department of Reproductive Medicine, Affiliated Hospital of Shandong Second Medical University, Weifang, 261042, China.
School of Clinical Medicine, Shandong Second Medical University, Weifang, 261053, China.
Front Med. 2024 Dec;18(6):1054-1067. doi: 10.1007/s11684-024-1069-3. Epub 2024 Sep 27.
P21-activated kinase 5 (PAK5) belongs to the PAK-II subfamily, which is an important regulator of cell survival, adhesion, and motility. However, the functions of PAK5 in endometriosis remain unclear. Here, PAK5 is strikingly upregulated in endometriosis. Furthermore, the knockdown of PAK5 or its inhibitor GNE 2861 blocks the development of endometriosis, which is equally demonstrated in PAK5-knockout mice. In addition, PAK5 promotes glycolysis by enhancing the protein stability of pyruvate kinase 2 (PKM2) in endometriotic cells, which is a key enzyme for glucose metabolism. Moreover, the phosphorylation of PKM2 at Ser519 by PAK5 mediates endometriosis cell proliferation and metastasis. Collectively, PAK5 plays an indispensable role in endometriosis. Our findings demonstrate that PAK5 is an important target for the treatment of endometriosis.
p21激活激酶5（PAK5）属于PAK-II亚家族，是细胞存活、黏附和运动的重要调节因子。然而，PAK5在子宫内膜异位症中的功能仍不清楚。在此，PAK5在子宫内膜异位症中显著上调。此外，PAK5的敲低或其抑制剂GNE 2861可阻断子宫内膜异位症的发展，这在PAK5基因敲除小鼠中也得到了同样的证实。此外，PAK5通过增强子宫内膜异位症细胞中丙酮酸激酶2（PKM2）的蛋白质稳定性来促进糖酵解，PKM2是葡萄糖代谢的关键酶。此外，PAK5使PKM2的Ser519位点磷酸化，介导子宫内膜异位症细胞的增殖和转移。总之，PAK5在子宫内膜异位症中起着不可或缺的作用。我们的研究结果表明，PAK5是治疗子宫内膜异位症的重要靶点。
