ArticleMolecular therapy oncolytics2020
Monocarboxylate Transporter 4 Is a Therapeutic Target in Non-small Cell Lung Cancer with Aerobic Glycolysis Preference.
Article in Molecular therapy oncolytics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 35 citations in OpenAlex.
- MCT4 deficiency suppresses tumor incidence and metastasis by downregulating IGF1 expression and enhancing anti-tumor immunity.Communications biology · 2026Article
- Dynamic Metabolic States in TNBC: Orchestrating Spatiotemporal Adaptation and Therapy.Oncology research · 2026Review
- Article
- Lactate and lactylation in tumor immunity.Frontiers of medicine · 2025Review
- Unveiling Metabolic Signatures as Potential Biomarkers in Common Cancers: Insights from Lung, Breast, Colorectal, Liver, and Gastric Tumours.Biomolecules · 2025Review
- Article
- Review
- Energy Metabolism in Human Pluripotent Stem and Differentiated Cells Compared Using a Seahorse XF96 Extracellular Flux Analyzer.International journal of stem cells · 2024Article
- Exploring monocarboxylate transporter inhibition for cancer treatment.Exploration of targeted anti-tumor therapy · 2024Review
- Evaluating [International journal of molecular sciences · 2023Article
- Preclinical evaluation of Mito-LND, a targeting mitochondrial metabolism inhibitor, for glioblastoma treatment.Journal of translational medicine · 2023Article
- Circ_0000235 targets MCT4 to promote glycolysis and progression of bladder cancer by sponging miR-330-5p.Cell death discovery · 2023Article
- Immunohistochemical evaluation and prognostic value of monocarboxylate transporter 1 (MCT1) and 4 (MCT4) in T-cell non-Hodgkin lymphoma.Clinical and experimental medicine · 2023Article
- Monocarboxylate transporter 4 involves in energy metabolism and drug sensitivity in hypoxia.Scientific reports · 2023Article
- Transcription profiling of feline mammary carcinomas and derived cell lines reveals biomarkers and drug targets associated with metabolic and cell cycle pathways.Scientific reports · 2022Article
- KDM3A-mediated SP1 activates PFKFB4 transcription to promote aerobic glycolysis in osteosarcoma and augment tumor development.BMC cancer · 2022Article
- Lactate Transporter SLC16A3 (MCT4) as an Onco-Immunological Biomarker Associating Tumor Microenvironment and Immune Responses in Lung Cancer.International journal of general medicine · 2022Article
- Targeting glycolysis in non-small cell lung cancer: Promises and challenges.Frontiers in pharmacology · 2022Review
- Article
- Inhibition of Mitochondrial Metabolism Leads to Selective Eradication of Cells Adapted to Acidic Microenvironment.International journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Targeting metabolic reprogramming is an emerging strategy in cancer therapy. However, clinical attempts to target metabolic reprogramming have been proved to be challenging, with metabolic heterogeneity of cancer being one of many reasons that causes treatment failure. Here, we stratified non-small cell lung cancer (NSCLC) cells, mainly lung adenocarcinoma, based on their metabolic phenotypes and demonstrated that the aerobic glycolysis-preference NSCLC cell subtype was resistant to the OXPHOS-targeting inhibitors. We identified that monocarboxylate transporter 4 (MCT4), a lactate transporter, was highly expressed in the aerobic glycolysis-preference subtype with function supporting the proliferation of these cells. Glucose could induce the expression of MCT4 in these cells through a ΔNp63α and Sp1-dependent pathway. Next, we showed that knockdown of MCT4 increased intracellular lactate concentration and induced a reactive oxygen species (ROS)-dependent cellular apoptosis in the aerobic glycolysis-preference NSCLC cell subtype. By scanning a panel of monoclonal antibodies with MCT4 neutralizing activity, we further identified a MCT4 immunoglobulin M (IgM) monoclonal antibody showing capable anti-proliferation efficacy on the aerobic glycolysis-preference NSCLC cell subtype. Our findings indicate that the metabolic heterogeneity is a critical factor for NSCLC therapy and manipulating the expression or function of MCT4 can be an effective strategy in targeting the aerobic glycolysis-preference NSCLC cell subtype.
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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.