Low levels of AMPK promote epithelial-mesenchymal transition in lung cancer primarily through HDAC4- and HDAC5-mediated metabolic reprogramming
Open accessAbstract
AMP-activated protein kinase (AMPK) serves as a "supermetabolic regulator" that helps maintain cellular energy homeostasis. However, the role of AMPK in glucose metabolism reprogramming in lung cancer remains unclear. Here, our study shows that low AMPK expression correlates with metastasis and clinicopathologic parameters of non-small-cell lung cancer. Low AMPK significantly enhances the Warburg effect in HBE and A549 cells, which in turn induces the expression of mesenchymal markers and enhances their invasion and migration. At the mechanistic level, low AMPK up-regulates HK2 expression and glycolysis levels through HDAC4 and HDAC5. Collectively, our findings demonstrate that low AMPK-induced metabolism can promote epithelial-mesenchymal transition progression in normal bronchial epithelial cells and lung cancer cells, and increase the risk for tumour metastasis.
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In lung cancer, low levels of AMPK promote cell proliferation and tumour growth.
“In lung cancer, low levels of AMPK promote cell proliferation and tumour growth.”
From HDACs and the epigenetic plasticity of cancer cells: target the complexity (2022) · cites this paper as Feng et al., 2020
The upregulation of HK2 in cells in which AMPK is downregulated depends on HDAC4 and HDAC5.
“The upregulation of HK2 in cells in which AMPK is downregulated depends on HDAC4 and HDAC5 in an undefined manner (Feng et al., 2020).”
From HDACs and the epigenetic plasticity of cancer cells: target the complexity (2022) · cites this paper as Feng et al., 2020
A decrease in AMPK affects EMT and metastasis in vivo.
“A decrease in AMPK affects EMT and metastasis in vivo.”
From HDACs and the epigenetic plasticity of cancer cells: target the complexity (2022) · cites this paper as Feng et al., 2020
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HDACs and the epigenetic plasticity of cancer cells: target the complexity
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- Authors
- Feng, S., Zhang, L., Liu, X., Li, G., Zhang, B., Wang, Z., Zhang, H., & Ma, H.
- Affiliations
- Xuzhou Medical College (CN)
- First Affiliated Hospital of Soochow University (CN)
- Corresponding author
- Zhang, Hao
- Ma, Haitao
- Venue
- Journal of Cellular and Molecular Medicine
- Publisher
- Wiley
- Published
- 2020-06-09
- Volume
- 24
- Issue
- 14
- Pages
- 7789-7801
- ISSN
- 1582-1838 (ISSN-L)
- 1582-4934
- PMC
- PMC7348170
- OpenAlex
- W3033661561
- Cited by
- 28
- References
- 28
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 5 · 2022: 9 · 2021: 6
- FWCI
- 1.62
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Cellular and Molecular Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Natural Science Foundation of Jiangsu Province (BK20171178, BK20191174)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Keywords
- AMPK, epithelial-mesenchymal transition, non-small cell lung cancer, HDAC4, HDAC5, metabolic reprogramming, Warburg effect, glycolysis, HK2, tumour metastasis, cell migration and invasion, energy homeostasis
- MeSH terms
- Animals, Disease Models, Animal, Energy Metabolism, Glycolysis, Hexokinase, Histone Deacetylases, Humans, Lung Neoplasms, Mitochondria, Neoplasm Staging, Repressor Proteins, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Neoplastic, Apoptosis, Cell Line, Tumor, Mice, AMP-Activated Protein Kinases, Epithelial-Mesenchymal Transition, Heterografts, Cellular Reprogramming
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