PAK5-mediated PKM2 Phosphorylation is Critical for Anaerobic Glycolysis in Endometriosis

Overview

Journal Front Med

Specialty General Medicine

Date 2024 Sep 27

PMID 39331255

Authors

Jiayi Lu

Xiaoyun Wang

Xiaodan Shi

Junyi Jiang

Lan Liu

Lu Liu

Chune Ren

Chao Lu

Zhenhai Yu

Affiliations

Soon will be listed here.

Abstract

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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