PAK5 介导的 PKM2 磷酸化对子宫内膜异位症中的无氧糖酵解至关重要。

IF 3.9 3区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Frontiers of Medicine Pub Date : 2024-12-01 Epub Date: 2024-09-27 DOI:10.1007/s11684-024-1069-3

Jiayi Lu, Xiaoyun Wang, Xiaodan Shi, Junyi Jiang, Lan Liu, Lu Liu, Chune Ren, Chao Lu, Zhenhai Yu

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引用次数: 0

摘要

P21激活激酶5（PAK5）属于PAK-II亚家族，是细胞存活、粘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。在本研究中，PAK5在子宫内膜异位症中显著上调。此外，PAK5或其抑制剂GNE 2861的敲除可阻止子宫内膜异位症的发生，这一点在PAK5基因敲除小鼠中同样得到了证实。此外，PAK5 通过增强子宫内膜异位症细胞中丙酮酸激酶 2（PKM2）蛋白的稳定性来促进糖酵解，而丙酮酸激酶 2 是葡萄糖代谢的关键酶。此外，PAK5 使 PKM2 在 Ser519 处磷酸化，介导了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扮演着不可或缺的角色。我们的研究结果表明，PAK5 是治疗子宫内膜异位症的一个重要靶点。

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PAK5-mediated PKM2 phosphorylation is critical for anaerobic glycolysis in endometriosis.

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.

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来源期刊

Frontiers of Medicine ONCOLOGYMEDICINE, RESEARCH & EXPERIMENTAL&-MEDICINE, RESEARCH & EXPERIMENTAL

CiteScore

18.30

自引率

0.00%

发文量

800

期刊介绍： Frontiers of Medicine is an international general medical journal sponsored by the Ministry of Education of China. The journal is jointly published by the Higher Education Press and Springer. Since the first issue of 2010, this journal has been indexed in PubMed/MEDLINE. Frontiers of Medicine is dedicated to publishing original research and review articles on the latest advances in clinical and basic medicine with a focus on epidemiology, traditional Chinese medicine, translational research, healthcare, public health and health policies.