ArticleThe Prostate2013
Malate dehydrogenase 2 confers docetaxel resistance via regulations of JNK signaling and oxidative metabolism.
Article in The Prostate, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 81 citations in OpenAlex.
- MDH2 S246 phosphorylation protects mitochondria against hypoxia/reoxygenation injury due to acetate/lactate metabolism.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2026Article
- Profiling the Complexity of Resistance Factors in Cancer Cells Towards Berberine and Its Derivatives.Pharmaceuticals (Basel, Switzerland) · 2025Article
- WSSV-induced reversal of the malate-aspartate shuttle facilitates viral replication in shrimp hemocytes.Cell communication and signaling : CCS · 2025Article
- β-Hydroxybutyrate enhances malate dehydrogenase 2 β-hydroxybutyrylation to alleviate hepatic steatosis in MASLD.Cellular and molecular life sciences : CMLS · 2025Article
- Understanding Enzalutamide-Resistance Based on a Functional Single-Cell Approach.The Prostate · 2025Article
- Deciphering Proteoform Landscape of Mammary Carcinoma by Top-Down Proteomics.Journal of proteome research · 2025Article
- Multi-Omics Insights into the Impact of MDH2 on Breast Cancer Progression: A Promising Druggable Target.Oncology research · 2025Article
- MDH2 Promotes Hepatocellular Carcinoma Growth Through Ferroptosis Evasion via Stabilizing GPX4.International journal of molecular sciences · 2024Article
- Cytosolic RNA binding of the mitochondrial TCA cycle enzyme malate dehydrogenase.RNA (New York, N.Y.) · 2024Article
- Proteomic-based stratification of intermediate-risk prostate cancer patients.Life science alliance · 2024Article
- Emerging proteins involved in castration‑resistant prostate cancer via the AR‑dependent and AR‑independent pathways (Review).International journal of oncology · 2023Review
- Article
- Genetics of enzymatic dysfunctions in metabolic disorders and cancer.Frontiers in oncology · 2023Review
- The impact of RNA binding proteins and the associated long non-coding RNAs in the TCA cycle on cancer pathogenesis.RNA biology · 2023Review
- Palmitoylation of MDH2 by ZDHHC18 activates mitochondrial respiration and accelerates ovarian cancer growth.Science China. Life sciences · 2022Article
- Review
- Targeting the Intrinsic Apoptosis Pathway: A Window of Opportunity for Prostate Cancer.Cancers · 2021Review
- LW1497, an Inhibitor of Malate Dehydrogenase, Suppresses TGF-β1-Induced Epithelial-Mesenchymal Transition in Lung Cancer Cells by Downregulating Slug.Antioxidants (Basel, Switzerland) · 2021Article
- A fragment-based approach identifies an allosteric pocket that impacts malate dehydrogenase activity.Communications biology · 2021Article
- Urinary malate dehydrogenase 2 is a new biomarker for early detection of non-small-cell lung cancer.Cancer science · 2021Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundResistance to chemotherapy represents a significant obstacle in prostate cancer therapeutics. Novel mechanistic understandings in cancer cell chemotherapeutic sensitivity and resistance can optimize treatment and improve patient outcome. Molecular alterations in the metabolic pathways are associated with cancer development; however, the role of these alterations in chemotherapy efficacy is largely unknown.
methodsIn a bed-side to bench-side reverse translational approach, we used cDNA microarray and qRT-PCR to identify genes that are associated with biochemical relapse after chemotherapy. Further, we tested the function of these genes in cell proliferation, metabolism, and chemosensitivity in prostate cancer cell lines.
resultsWe report that the gene encoding mitochondrial malate dehydrogenase 2 (MDH2) is overexpressed in clinical prostate cancer specimens. Patients with MDH2 overexpression had a significantly shorter period of relapse-free survival (RFS) after undergoing neoadjuvant chemotherapy. To understand the molecular mechanism underlying this clinical observation, we observed that MDH2 expression was elevated in prostate cancer cell lines compared to benign prostate epithelial cells. Stable knockdown of MDH2 via shRNA in prostate cancer cell lines decreased cell proliferation and increased docetaxel sensitivity. Further, MDH2 shRNA enhanced docetaxel-induced activations of JNK signaling and induced metabolic inefficiency.
conclusionTaken together, these data suggest a novel function for MDH2 in prostate cancer development and chemotherapy resistance, in which MDH2 regulates chemotherapy-induced signal transduction and oxidative metabolism.
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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.