ArticleNeoplasia (New York, N.Y.)2019
Metformin Regulates the Expression of CD133 Through the AMPK-CEBPβ Pathway in Hepatocellular Carcinoma Cell Lines.
Article in Neoplasia (New York, N.Y.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 44 citations in OpenAlex.
- Phosphoenolpyruvate carboxykinase 2 activation of the AMPK-CEBPB axis to enhance glutamine utilization to promote glycolysis and malignant behavior in adenocarcinomas cells under glucose deprivation.Journal of cell communication and signaling · 2026Article
- C/EBP-β Mediates the Reversal of Sorafenib Resistance by Tunicamycin in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2026Article
- Research Progress on the Molecular Mechanism of Metformin Regulating AMPK Signaling Pathway in Inhibiting Liver Cancer.OncoTargets and therapy · 2026Review
- CEBPB emerges as a key regulatory factor in human cancers through diverse molecular mechanisms and clinical implications.Discover oncology · 2025Review
- Hepatocellular carcinoma stem cells: the current state of small molecule-based inhibitors.Cell death & disease · 2025Review
- Traditional Chinese Medicine and renal regeneration: experimental evidence and future perspectives.Chinese medicine · 2024Review
- The strategies to cure cancer patients by eradicating cancer stem-like cells.Molecular cancer · 2023Review
- Analysis of differential membrane proteins related to matrix stiffness-mediated metformin resistance in hepatocellular carcinoma cells.Proteome science · 2023Article
- Chrysin 7-O-β-d-glucopyranoside increases hepatic low-density lipoprotein receptor expression through AMP-activated protein kinase activation.FEBS open bio · 2023Article
- Empagliflozin: a potential anticancer drug.Discover oncology · 2023Review
- Unmasking the Deceptive Nature of Cancer Stem Cells: The Role of CD133 in Revealing Their Secrets.International journal of molecular sciences · 2023Review
- Mycochemicals against Cancer Stem Cells.Toxins · 2023Review
- PGAM1 regulation of ASS1 contributes to the progression of breast cancer through the cAMP/AMPK/CEBPB pathway.Molecular oncology · 2022Article
- Metformin inhibits human non-small cell lung cancer by regulating AMPK-CEBPB-PDL1 signaling pathway.Cancer immunology, immunotherapy : CII · 2022Article
- Metformin and Cancer, an Ambiguanidous Relationship.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Role of metformin in the diagnosis, prevention, and treatment of hepatocellular carcinoma.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2022Article
- The role of CD133 in hepatocellular carcinoma.Cancer biology & therapy · 2021Article
- C/EBPβ regulates the JAK/STAT signaling pathway in triple-negative breast cancer.FEBS open bio · 2021Article
- Green Synthesized Honokiol Transfersomes Relieve the Immunosuppressive and Stem-Like Cell Characteristics of the Aggressive B16F10 Melanoma.International journal of nanomedicine · 2021Article
- AMP-Activated Protein Kinase: Do We Need Activators or Inhibitors to Treat or Prevent Cancer?International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CD133 is a cellular surface protein, which has been reported to be a cancer stem cell marker, and thus is considered a potential target for cancer treatment. Metformin, one of the biguanides used for the treatment of diabetes, is also known to reduce the risk of cancer development and cancer stem-like cells (CSCs), including the expression of CD133. However, the mechanism underlying the reduction of the expression of CD133 by metformin is not yet understood. This study shows that metformin suppressed CD133 expression mainly by affecting the CD133 P1 promoter via adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling but not the mammalian target of rapamycin (mTOR). AMPK inhibition rescued the reduction of CD133 by metformin. Further experiments demonstrated that CCAAT/enhancer-binding protein beta (CEBPβ) was upregulated by metformin and that two isoforms of CEBPβ reciprocally regulated the expression of CD133. Specifically, the liver-enriched activator protein (LAP) isoform increased the expression of CD133 by directly binding to the P1 promoter region, whereas the liver-enriched inhibitory protein (LIP) isoform suppressed the expression of CD133. Consistent with these findings, a three dimensional (3D) culture assay and drug sensitivity assay demonstrated that LAP-overexpressing cells formed large spheroids and were more resistant to 5-fluorouracil (5-FU) treatment, whereas LIP-overexpressing cells were more sensitive to 5-FU and showed combined effects with metformin. Our results indicated that metformin-AMPK-CEBPβ signaling plays a crucial role in regulating the gene expression of CD133. Additionally, regulating the ratio of LAP/LIP may be a novel strategy for targeting CSCs for the treatment of cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.