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ECHDC2 inhibits the proliferation of gastric cancer cells by binding with NEDD4 to degrade MCCC2 and reduce aerobic glycolysis
by
He, Jiancheng
, Ji, Li
, Xue, Wanjiang
, Dai, Lingchen
, Chen, Yu
, Yi, Jianfeng
in
Aerobic glycolysis
/ Animals
/ Biomedical and Life Sciences
/ Biomedicine
/ Cell growth
/ Cell Line, Tumor
/ Cell Proliferation
/ Datasets
/ Dehydrogenases
/ ECHDC2
/ Enoyl-CoA Hydratase - genetics
/ Enoyl-CoA Hydratase - metabolism
/ Enzymes
/ Fatty acids
/ Female
/ Gastric cancer
/ Gene Expression Regulation, Neoplastic
/ Glycolysis
/ Humans
/ Kinases
/ Lymphatic system
/ Male
/ MCCC2
/ Medical prognosis
/ Metabolism
/ Metastasis
/ Mice
/ Mice, Nude
/ Molecular Medicine
/ NEDD4
/ Nedd4 Ubiquitin Protein Ligases - genetics
/ Nedd4 Ubiquitin Protein Ligases - metabolism
/ Oxidation
/ Protein Binding
/ Proteolysis
/ Regression analysis
/ Research Article
/ Stomach Neoplasms - genetics
/ Stomach Neoplasms - metabolism
/ Stomach Neoplasms - pathology
/ Ubiquitination
/ Warburg Effect, Oncologic
2024
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ECHDC2 inhibits the proliferation of gastric cancer cells by binding with NEDD4 to degrade MCCC2 and reduce aerobic glycolysis
by
He, Jiancheng
, Ji, Li
, Xue, Wanjiang
, Dai, Lingchen
, Chen, Yu
, Yi, Jianfeng
in
Aerobic glycolysis
/ Animals
/ Biomedical and Life Sciences
/ Biomedicine
/ Cell growth
/ Cell Line, Tumor
/ Cell Proliferation
/ Datasets
/ Dehydrogenases
/ ECHDC2
/ Enoyl-CoA Hydratase - genetics
/ Enoyl-CoA Hydratase - metabolism
/ Enzymes
/ Fatty acids
/ Female
/ Gastric cancer
/ Gene Expression Regulation, Neoplastic
/ Glycolysis
/ Humans
/ Kinases
/ Lymphatic system
/ Male
/ MCCC2
/ Medical prognosis
/ Metabolism
/ Metastasis
/ Mice
/ Mice, Nude
/ Molecular Medicine
/ NEDD4
/ Nedd4 Ubiquitin Protein Ligases - genetics
/ Nedd4 Ubiquitin Protein Ligases - metabolism
/ Oxidation
/ Protein Binding
/ Proteolysis
/ Regression analysis
/ Research Article
/ Stomach Neoplasms - genetics
/ Stomach Neoplasms - metabolism
/ Stomach Neoplasms - pathology
/ Ubiquitination
/ Warburg Effect, Oncologic
2024
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ECHDC2 inhibits the proliferation of gastric cancer cells by binding with NEDD4 to degrade MCCC2 and reduce aerobic glycolysis
by
He, Jiancheng
, Ji, Li
, Xue, Wanjiang
, Dai, Lingchen
, Chen, Yu
, Yi, Jianfeng
in
Aerobic glycolysis
/ Animals
/ Biomedical and Life Sciences
/ Biomedicine
/ Cell growth
/ Cell Line, Tumor
/ Cell Proliferation
/ Datasets
/ Dehydrogenases
/ ECHDC2
/ Enoyl-CoA Hydratase - genetics
/ Enoyl-CoA Hydratase - metabolism
/ Enzymes
/ Fatty acids
/ Female
/ Gastric cancer
/ Gene Expression Regulation, Neoplastic
/ Glycolysis
/ Humans
/ Kinases
/ Lymphatic system
/ Male
/ MCCC2
/ Medical prognosis
/ Metabolism
/ Metastasis
/ Mice
/ Mice, Nude
/ Molecular Medicine
/ NEDD4
/ Nedd4 Ubiquitin Protein Ligases - genetics
/ Nedd4 Ubiquitin Protein Ligases - metabolism
/ Oxidation
/ Protein Binding
/ Proteolysis
/ Regression analysis
/ Research Article
/ Stomach Neoplasms - genetics
/ Stomach Neoplasms - metabolism
/ Stomach Neoplasms - pathology
/ Ubiquitination
/ Warburg Effect, Oncologic
2024
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ECHDC2 inhibits the proliferation of gastric cancer cells by binding with NEDD4 to degrade MCCC2 and reduce aerobic glycolysis
Journal Article
ECHDC2 inhibits the proliferation of gastric cancer cells by binding with NEDD4 to degrade MCCC2 and reduce aerobic glycolysis
2024
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Overview
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.
Publisher
BioMed Central,Springer Nature B.V,BMC
Subject
/ Animals
/ Biomedical and Life Sciences
/ Datasets
/ ECHDC2
/ Enoyl-CoA Hydratase - genetics
/ Enoyl-CoA Hydratase - metabolism
/ Enzymes
/ Female
/ Gene Expression Regulation, Neoplastic
/ Humans
/ Kinases
/ Male
/ MCCC2
/ Mice
/ NEDD4
/ Nedd4 Ubiquitin Protein Ligases - genetics
/ Nedd4 Ubiquitin Protein Ligases - metabolism
/ Stomach Neoplasms - genetics
/ Stomach Neoplasms - metabolism
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