ArticleScientific reports2021
MCT4 is induced by metastasis-enhancing pathogenic mitochondrial NADH dehydrogenase gene mutations and can be a therapeutic target.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 15 citations in OpenAlex.
- Metabolic marker profiling of circulating tumour cells in NSCLC patients treated with osimertinib: focus on MCT1 and MCT4.Therapeutic advances in medical oncology · 2026Article
- One-step Radiosynthesis and Preclinical Evaluation of Molecular Tracer [Molecular imaging and biology · 2025Article
- Expression of nuclear receptors and glucose metabolic pathway proteins in sebaceous carcinoma: Androgen receptor and monocarboxylate transporter 1 have a key role in disease progression.Oncology letters · 2024Article
- ENO2, a Glycolytic Enzyme, Contributes to Prostate Cancer Metastasis: A Systematic Review of Literature.Cancers · 2024Review
- SYVN1-mediated ubiquitylation directs localization of MCT4 in the plasma membrane to promote the progression of lung adenocarcinoma.Cell death & disease · 2023Article
- MCT4-dependent lactate secretion suppresses antitumor immunity in LKB1-deficient lung adenocarcinoma.Cancer cell · 2023Article
- Antiproliferative effects of mitochondria-targeted N-acetylcysteine and analogs in cancer cells.Scientific reports · 2023Article
- Monocarboxylate transporter 4 involves in energy metabolism and drug sensitivity in hypoxia.Scientific reports · 2023Article
- Suppression of non-small-cell lung cancer A549 tumor growth by an mtDNA mutation-targeting pyrrole-imidazole polyamide-triphenylphosphonium and a senolytic drug.Cancer science · 2022Article
- New horizons in modulating the radio-sensitivity of head and neck cancer - 100 years after Warburg' effect discovery.Frontiers in oncology · 2022Review
- Targeting glycolysis in non-small cell lung cancer: Promises and challenges.Frontiers in pharmacology · 2022Review
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Authors and funding
7 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Pathogenic mitochondrial NADH dehydrogenase (ND) gene mutations enhance the invasion and metastasis of various cancer cells, and they are associated with metastasis in human non-small cell lung cancer (NSCLC). Moreover, monocarboxylate transporter 4 (MCT4) is overexpressed in solid cancers and plays a role in cancer cell proliferation and survival. Here, we report that MCT4 is exclusively expressed in mouse transmitochondrial cybrids with metastasis-enhancing pathogenic ND6 mutations. A high level of MCT4 is also detected in human NSCLC cell lines and tissues predicted to carry pathogenic ND mutations and is associated with poor prognosis in NSCLC patients. MCT4 expression in the cell lines is suppressed by N-acetyl-L-cysteine. Phosphatidylinositol-3 kinase (PI3K), AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin (mTOR) are involved in the regulation of MCT4 expression in the transmitochondrial cybrid cells. An MCT1/4 inhibitor effectively kills NSCLC cells with predicted pathogenic ND mutations, but an MCT1/2 inhibitor does not have the same effect. Thus, MCT4 expression is augmented by pathogenic ND mutations and could be a biomarker and a therapeutic target in pathogenic ND mutation-harbouring metastatic tumours.
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