Eno1, also known as α -Enolase or 2 -phospho -D -glycerate hydrolase, is a glycolytic enzyme. It catalyzes the conversion of 2 -phosphoglyceric acid to phosphoenolpyruvic acid during glycolysis, playing a crucial role in the Warburg effect [1,9]. Eno1 is involved in multiple pathways related to cancer development, such as regulating cellular energetic, tumor proliferation, apoptosis, immune evasion, and angiogenesis [1]. Genetic models like gene knockout (KO) or conditional knockout (CKO) mouse models are valuable for studying its functions.

In in vivo studies, knockdown of Eno1 decreased cancer cell proliferation and invasiveness in lung cancer models, indicating its role in promoting metastasis via HGFR and WNT signaling-driven epithelial-to-mesenchymal transition [5]. In hepatocellular carcinoma, Eno1 suppresses cancer cell ferroptosis by degrading the mRNA of iron regulatory protein 1 [4]. In liver carcinogenesis, Eno1 promotes tumorigenesis through YAP1-dependent arachidonic acid metabolism [2]. In hypoxic pulmonary hypertension, inhibition of Eno1 in endothelial cells restored hypoxia-induced endothelial dysfunction, suggesting its role in the pathogenesis [3]. In colorectal cancer, targeting the Eno1 pathway may be meaningful as Fusobacterium nucleatum activates lncRNA ENO1-IT1 to promote glycolysis and oncogenesis [6]. In bladder cancer, melatonin inhibits tumorigenesis by suppressing PPARγ/ENO1-mediated glycolysis, and Eno1 could be a predictive biomarker [7]. In colorectal cancer, the NSUN2/YBX1/m5C-ENO1 positive feedback loop promotes tumor progression through metabolic recoding [8].

In conclusion, Eno1 is a multifunctional protein with its glycolytic function being essential in cellular energy regulation. Model-based research, especially KO/CKO mouse models, has revealed its significant roles in cancer development, including promoting tumor proliferation, invasion, metastasis, and evading cell death mechanisms. Understanding Eno1's functions provides potential therapeutic targets for treating various cancers.

References:

1. Huang, Chen Kai, Sun, Ying, Lv, Lei, Ping, Yong. 2022. ENO1 and Cancer. In Molecular therapy oncolytics, 24, 288-298. doi:10.1016/j.omto.2021.12.026. https://pubmed.ncbi.nlm.nih.gov/35434271/

2. Sun, Linchong, Suo, Caixia, Zhang, Tong, Zhang, Huafeng, Gao, Ping. 2023. ENO1 promotes liver carcinogenesis through YAP1-dependent arachidonic acid metabolism. In Nature chemical biology, 19, 1492-1503. doi:10.1038/s41589-023-01391-6. https://pubmed.ncbi.nlm.nih.gov/37500770/

3. Shi, Yuqing, Liu, Jie, Zhang, Ruoyang, Sun, Ying, Wang, Chen. 2023. Targeting Endothelial ENO1 (Alpha-Enolase) -PI3K-Akt-mTOR Axis Alleviates Hypoxic Pulmonary Hypertension. In Hypertension (Dallas, Tex. : 1979), 80, 1035-1047. doi:10.1161/HYPERTENSIONAHA.122.19857. https://pubmed.ncbi.nlm.nih.gov/37075135/

4. Zhang, Tong, Sun, Linchong, Hao, Yijie, Gao, Ping, Zhang, Huafeng. 2021. ENO1 suppresses cancer cell ferroptosis by degrading the mRNA of iron regulatory protein 1. In Nature cancer, 3, 75-89. doi:10.1038/s43018-021-00299-1. https://pubmed.ncbi.nlm.nih.gov/35121990/

5. Li, Hsin-Jung, Ke, Feng-Yi, Lin, Chia-Ching, Yang, Pan-Chyr, Wu, Han-Chung. 2021. ENO1 Promotes Lung Cancer Metastasis via HGFR and WNT Signaling-Driven Epithelial-to-Mesenchymal Transition. In Cancer research, 81, 4094-4109. doi:10.1158/0008-5472.CAN-20-3543. https://pubmed.ncbi.nlm.nih.gov/34145039/

6. Hong, Jie, Guo, Fangfang, Lu, Shi-Yuan, Chen, Haoyan, Fang, Jing-Yuan. 2020. F. nucleatum targets lncRNA ENO1-IT1 to promote glycolysis and oncogenesis in colorectal cancer. In Gut, 70, 2123-2137. doi:10.1136/gutjnl-2020-322780. https://pubmed.ncbi.nlm.nih.gov/33318144/

7. Shen, Dexin, Deng, Zhao, Liu, Wei, Xiao, Yu, Wang, Xinghuan. 2023. Melatonin inhibits bladder tumorigenesis by suppressing PPARγ/ENO1-mediated glycolysis. In Cell death & disease, 14, 246. doi:10.1038/s41419-023-05770-8. https://pubmed.ncbi.nlm.nih.gov/37024456/

8. Chen, Baoxiang, Deng, Yanrong, Hong, Yuntian, Zhao, Jianhong, Jiang, Congqing. 2024. Metabolic Recoding of NSUN2-Mediated m5C Modification Promotes the Progression of Colorectal Cancer via the NSUN2/YBX1/m5C-ENO1 Positive Feedback Loop. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 11, e2309840. doi:10.1002/advs.202309840. https://pubmed.ncbi.nlm.nih.gov/38769664/

9. Li, Yafei, Liu, Lu, Li, Bo. 2024. Role of ENO1 and its targeted therapy in tumors. In Journal of translational medicine, 22, 1025. doi:10.1186/s12967-024-05847-8. https://pubmed.ncbi.nlm.nih.gov/39543641/