2. Academic Validation
  3. MYG1 drives glycolysis and colorectal cancer development through nuclear-mitochondrial collaboration

MYG1 drives glycolysis and colorectal cancer development through nuclear-mitochondrial collaboration

  • Nat Commun. 2024 Jun 11;15(1):4969. doi: 10.1038/s41467-024-49221-0.
Jianxiong Chen # 1 2,  Shiyu Duan # 1 2,  Yulu Wang 1 2,  Yuping Ling 1 2,  Xiaotao Hou 1 2,  Sijing Zhang 1 2,  Xunhua Liu 1 2,  Xiaoli Long 1 2,  Jiawen Lan 1 2,  Miao Zhou 2,  Huimeng Xu 1 2,  Haoxuan Zheng 3,  Jun Zhou 4 5
Affiliations

Affiliations

  • 1 Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
  • 2 Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.
  • 3 Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. ryan801218@163.com.
  • 4 Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. jhzhou@smu.edu.cn.
  • 5 Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China. jhzhou@smu.edu.cn.
  • # Contributed equally.
PMID: 38862489 DOI: 10.1038/s41467-024-49221-0
Abstract

Metabolic remodeling is a strategy for tumor survival under stress. However, the molecular mechanisms during the metabolic remodeling of colorectal Cancer (CRC) remain unclear. Melanocyte proliferating gene 1 (MYG1) is a 3'-5' RNA exonuclease and plays a key role in mitochondrial functions. Here, we uncover that MYG1 expression is upregulated in CRC progression and highly expressed MYG1 promotes glycolysis and CRC progression independent of its exonuclease activity. Mechanistically, nuclear MYG1 recruits HSP90/GSK3β complex to promote PKM2 phosphorylation, increasing its stability. PKM2 transcriptionally activates MYC and promotes MYC-medicated glycolysis. Conversely, c-Myc also transcriptionally upregulates MYG1, driving the progression of CRC. Meanwhile, mitochondrial MYG1 on the one hand inhibits Oxidative Phosphorylation (OXPHOS), and on the other hand blocks the release of Cyt c from mitochondria and inhibits cell Apoptosis. Clinically, patients with KRAS mutation show high expression of MYG1, indicating a high level of glycolysis and a poor prognosis. Targeting MYG1 may disturb metabolic balance of CRC and serve as a potential target for the diagnosis and treatment of CRC.

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