ArticleScientific reports2023
Monocarboxylate transporter 4 involves in energy metabolism and drug sensitivity in hypoxia.
Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 17 citations in OpenAlex.
- Cancer-derived lactic acid as a potential upstream contributor to tumor hypoxia.Communications biology · 2026Review
- Lactylation in cancer: molecular mechanisms and advances in clinical study.Molecular cancer · 2026Review
- Targeted metabolism creates possibilities for lung cancer treatment in the precision tumor era.Respiratory research · 2026Review
- A mechanovascular framework for pre-neoplastic microenvironmental dysregulation and early carcinogenesis.Frontiers in oncology · 2026Article
- HIF-1α-centered metabolic reprogramming in osteoarthritis: cell type-specific effects and intercellular crosstalk among chondrocytes, BMSCs, and macrophages.Frontiers in immunology · 2026Review
- Lactate metabolism and protein lactylation in colorectal cancer: from metabolic reprogramming to epigenetic regulation.Frontiers in oncology · 2026Review
- The symbiotic axis between the acidic tumor microenvironment and cancer stem cells: a driver of malignancy and therapeutic resistance.Frontiers in oncology · 2026Review
- Hypoxic tumor microenvironment and immune cell dynamics: From metabolic reprogramming to therapeutic innovation.Iranian journal of basic medical sciences · 2026Review
- Targeting ubiquitin-specific protease 14 reduces metastatic potential and metabolic activity in cervical cancer via direct modulation of monocarboxylate transporter-4.Journal of translational medicine · 2025Article
- Targeting lactic acidosis in the tumor microenvironment: Enhancing TACE efficacy in hepatocellular carcinoma.Liver research (Beijing, China) · 2025Review
- Review
- Polarization of Tumor Cells and Tumor-Associated Macrophages: Molecular Mechanisms and Therapeutic Targets.MedComm · 2025Review
- The emerging role of glycolysis and immune evasion in ovarian cancer.Cancer cell international · 2025Review
- Lactate and lactylation in cancer.Signal transduction and targeted therapy · 2025Review
- Sulfated and Glucuronidated Conjugates of 3-(4-Hydroxy-3-methoxyphenyl) Propionic Acid Can Promote NO Production by Elevated CaACS omega · 2025Article
- Ferroptosis in ischemia-reperfusion injury: molecular mechanisms and therapeutic strategies.American journal of cardiovascular disease · 2025Review
- Microbial metabolites in tumor metabolic reprogramming and immunotherapy: new insights.Frontiers in cellular and infection microbiology · 2025Review
- Hypoxia and activation of hypoxia inducible factor alpha as influencers of inflammatory helper T cells in autoimmune disease - a link between cancer and autoimmunity.Frontiers in immunology · 2025Review
- Regulatory role and therapeutic prospect of lactate modification in cancer.Frontiers in pharmacology · 2025Review
- Altered metabolism in cancer: insights into energy pathways and therapeutic targets.Molecular cancer · 2024Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metabolic reprogramming of cancer cells is a potential target for cancer therapy. It is also known that a hypoxic environment, one of the tumor microenvironments, can alter the energy metabolism from oxidative phosphorylation to glycolysis. However, the relationship between hypoxia and drug sensitivity, which targets energy metabolism, is not well known. In this study, A549 cells, a cell line derived from lung adenocarcinoma, were evaluated under normoxia and hypoxia for the sensitivity of reagents targeting oxidative phosphorylation (metformin) and glycolysis (α-cyano-4-hydroxycinnamic acid [CHC]). The results showed that a hypoxic environment increased the expression levels of monocarboxylate transporter (MCT) 4 and hypoxia-induced factor-1α (HIF-1α), whereas MCT1 and MCT2 expression did not vary between normoxia and hypoxia. Furthermore, the evaluation of the ATP production ratio indicated that glycolysis was enhanced under hypoxic conditions. It was then found that the sensitivity to metformin decreased while that to CHC increased under hypoxia. To elucidate this mechanism, MCT4 and HIF-1α were knocked down and the expression level of MCT4 was significantly decreased under both conditions. In contrast, the expression of HIF-1α was decreased by HIF-1α knockdown and increased by MCT4 knockdown. In addition, changes in metformin and CHC sensitivity under hypoxia were eliminated by the knockdown of MCT4 and HIF-1α, suggesting that MCT4 is involved in the phenomenon described above. In conclusion, it was shown that the sensitivity of reagents targeting energy metabolism is dependent on their microenvironment. As MCT4 is involved in some of these mechanisms, we hypothesized that MCT4 could be an important target molecule for cancer therapy.
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