https://scholars.lib.ntu.edu.tw/handle/123456789/523421
Title: | Monocarboxylate Transporter 4 Is a Therapeutic Target in Non-small Cell Lung Cancer with Aerobic Glycolysis Preference | Authors: | TING-CHUN KUO Huang K.-Y. Yang S.-C. Wu S. Chung W.-C. YIH-LEONG CHANG Hong T.-M. Wang S.-P. Chen H.-Y. Hsiao T.-H. PAN-CHYR YANG |
Issue Date: | 2020 | Publisher: | Cell Press | Journal Volume: | 18 | Start page/Pages: | 189-201 | Source: | Molecular Therapy - Oncolytics | 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. ? 2020 The Author(s)Yang and colleagues stratified NSCLC cells based on their metabolic phenotypes and identified that monocarboxylate transporter 4 (MCT4) was highly expressed in the aerobic glycolysis-preference subtype with function supporting the proliferation of these cells. Additionally, they discovered a MCT4-neutralizing antibody with cell-inhibitory activity on this aerobic glycolysis-preference NSCLC cell subtype. ? 2020 The Author(s) |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85087815278&doi=10.1016%2fj.omto.2020.06.012&partnerID=40&md5=93d32f90997a1d93134f23637b113b49 https://scholars.lib.ntu.edu.tw/handle/123456789/523421 |
ISSN: | 2372-7705 | DOI: | 10.1016/j.omto.2020.06.012 | SDG/Keyword: | immunoglobulin M; monocarboxylate transporter 4; monoclonal antibody; aerobic glycolysis; antibody production; apoptosis; Article; cancer resistance; cell heterogeneity; cell proliferation; human; human cell; lung adenocarcinoma cell line; non small cell lung cancer; priority journal; protein expression |
Appears in Collections: | 醫學系 |
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