2. Academic Validation
  3. The moonlighting function of glycolytic enzyme enolase-1 promotes choline phospholipid metabolism and tumor cell proliferation

The moonlighting function of glycolytic enzyme enolase-1 promotes choline phospholipid metabolism and tumor cell proliferation

  • Proc Natl Acad Sci U S A. 2023 Apr 11;120(15):e2209435120. doi: 10.1073/pnas.2209435120.
Qingxia Ma 1,  Hongfei Jiang 1,  Leina Ma 1,  Gaoxiang Zhao 1,  Qianqian Xu 1,  Dong Guo 2,  Ningning He 1,  Hao Liu 3,  Zhaoyuan Meng 1,  Juanjuan Liu 1,  Lei Zhu 1,  Qian Lin 1,  Xiaolin Wu 1 4,  Min Li 2,  Shudi Luo 2,  Jing Fang 1,  Zhimin Lu 2 5
Affiliations

Affiliations

  • 1 Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao Cancer Institute, Qingdao, Shandong 266000, China.
  • 2 Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310029, China.
  • 3 Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
  • 4 Department of Orthopedics, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China.
  • 5 Zhejinag University Cancer Center, Hangzhou, Zhejiang 310029, China.
PMID: 37011206 DOI: 10.1073/pnas.2209435120
Abstract

Aberrantly upregulated choline phospholipid metabolism is a novel emerging hallmark of Cancer, and choline kinase α (CHKα), a key Enzyme for phosphatidylcholine production, is overexpressed in many types of human Cancer through undefined mechanisms. Here, we demonstrate that the expression levels of the glycolytic Enzyme enolase-1 (ENO1) are positively correlated with CHKα expression levels in human glioblastoma specimens and that ENO1 tightly governs CHKα expression via posttranslational regulation. Mechanistically, we reveal that both ENO1 and the ubiquitin E3 Ligase TRIM25 are associated with CHKα. Highly expressed ENO1 in tumor cells binds to I199/F200 of CHKα, thereby abrogating the interaction between CHKα and TRIM25. This abrogation leads to the inhibition of TRIM25-mediated polyubiquitylation of CHKα at K195, increased stability of CHKα, enhanced choline metabolism in glioblastoma cells, and accelerated brain tumor growth. In addition, the expression levels of both ENO1 and CHKα are associated with poor prognosis in glioblastoma patients. These findings highlight a critical moonlighting function of ENO1 in choline phospholipid metabolism and provide unprecedented insight into the integrated regulation of Cancer metabolism by crosstalk between glycolytic and lipidic Enzymes.

Keywords

CHKα; TRIM25; enolase.

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