2. Academic Validation
  3. ECHDC2 inhibits the proliferation of gastric cancer cells by binding with NEDD4 to degrade MCCC2 and reduce aerobic glycolysis

ECHDC2 inhibits the proliferation of gastric cancer cells by binding with NEDD4 to degrade MCCC2 and reduce aerobic glycolysis

  • Mol Med. 2024 May 23;30(1):69. doi: 10.1186/s10020-024-00832-9.
Jiancheng He # 1 2 3,  Jianfeng Yi # 1 2 3,  Li Ji 1 2 3,  Lingchen Dai 1 2 3,  Yu Chen 4 5 6,  Wanjiang Xue 7 8
Affiliations

Affiliations

  • 1 Department of Gastrointestinal Surgery, Affliated Hospital of Nantong University, Medical School of Nantong University, 20 Xisi Street, Nantong, 226001, China.
  • 2 Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, 226001, China.
  • 3 Nantong Key Laboratory of Gastrointestinal Oncology, Nantong, 226001, China.
  • 4 Department of Gastrointestinal Surgery, Affliated Hospital of Nantong University, Medical School of Nantong University, 20 Xisi Street, Nantong, 226001, China. 2113310109@stmail.ntu.edu.cn.
  • 5 Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, 226001, China. 2113310109@stmail.ntu.edu.cn.
  • 6 Nantong Key Laboratory of Gastrointestinal Oncology, Nantong, 226001, China. 2113310109@stmail.ntu.edu.cn.
  • 7 Department of Gastrointestinal Surgery, Affliated Hospital of Nantong University, Medical School of Nantong University, 20 Xisi Street, Nantong, 226001, China. xuewanjiang@ntu.edu.cn.
  • 8 Nantong Key Laboratory of Gastrointestinal Oncology, Nantong, 226001, China. xuewanjiang@ntu.edu.cn.
  • # Contributed equally.
PMID: 38783226 DOI: 10.1186/s10020-024-00832-9
Abstract

Background: The Enoyl-CoA hydratase/isomerase family plays a crucial role in the metabolism of tumors, being crucial for maintaining the energy balance and biosynthetic needs of Cancer cells. However, the Enzymes within this family that are pivotal in gastric Cancer (GC) remain unclear.

Methods: We employed bioinformatics techniques to identify key Enoyl-CoA hydratase/isomerase in GC. The expression of ECHDC2 and its clinical significance were validated through tissue microarray analysis. The role of ECHDC2 in GC was further assessed using colony formation assays, CCK8 assay, EDU assay, Glucose and lactic acid assay, and subcutaneous tumor experiments in nude mice. The mechanism of action of ECHDC2 was validated through Western blotting, Co-immunoprecipitation, and immunofluorescence experiments.

Results: Our analysis of multiple datasets indicates that low expression of ECHDC2 in GC is significantly associated with poor prognosis. Overexpression of ECHDC2 notably inhibits aerobic glycolysis and proliferation of GC cells both in vivo and in vitro. Further experiments revealed that overexpression of ECHDC2 suppresses the p38 MAPK pathway by inhibiting the protein level of MCCC2, thereby restraining glycolysis and proliferation in GC cells. Ultimately, it was discovered that ECHDC2 promotes the ubiquitination and subsequent degradation of MCCC2 protein by binding with NEDD4.

Conclusions: These findings underscore the pivotal role of the ECHDC2 in regulating aerobic glycolysis and proliferation in GC cells, suggesting ECHDC2 as a potential therapeutic target in GC.

Keywords

Aerobic glycolysis; ECHDC2; Gastric cancer; MCCC2; NEDD4; Ubiquitination.

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