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乳酸脱氢酶 A：致癌作用中的关键因子及癌症治疗中的潜在靶点。

Lactate dehydrogenase A: A key player in carcinogenesis and potential target in cancer therapy.

机构信息

Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.

State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, China.

出版信息

Cancer Med. 2018 Dec;7(12):6124-6136. doi: 10.1002/cam4.1820. Epub 2018 Nov 6.

DOI:10.1002/cam4.1820
PMID:30403008
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6308051/
Abstract

Elevated glycolysis remains a universal and primary character of cancer metabolism, which deeply depends on dysregulated metabolic enzymes. Lactate dehydrogenase A (LDHA) facilitates glycolytic process by converting pyruvate to lactate. Numerous researches demonstrate LDHA has an aberrantly high expression in multiple cancers, which is associated with malignant progression. In this review, we summarized LDHA function in cancer research. First, we gave an introduction of structure, location, and basic function of LDHA. Following, we discussed the transcription and activation mode of LDHA. Further, we focused on the function of LDHA in cancer bio-characteristics. Later, we discussed the clinical practice of LDHA in cancer prevention and treatment. What we discussed gives a precise insight into LDHA especially in cancer research, which will contribute to exploring cancer pathogenesis and its handling measures.

摘要

糖酵解升高仍然是癌症代谢的普遍和主要特征，这深深依赖于代谢酶的失调。乳酸脱氢酶 A（LDHA）通过将丙酮酸转化为乳酸来促进糖酵解过程。大量研究表明，LDHA在多种癌症中表达异常升高，与恶性进展相关。在这篇综述中，我们总结了 LDHA 在癌症研究中的功能。首先，我们介绍了 LDHA 的结构、位置和基本功能。其次，我们讨论了 LDHA 的转录和激活模式。进一步，我们专注于 LDHA 在癌症生物学特性中的功能。随后，我们讨论了 LDHA 在癌症预防和治疗中的临床实践。我们所讨论的内容为 LDHA 提供了一个精准的视角，特别是在癌症研究方面，这将有助于探索癌症发病机制和处理措施。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/629d/6308051/c99c464b0f1e/CAM4-7-6124-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/629d/6308051/cf3c1dbbd47e/CAM4-7-6124-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/629d/6308051/c99c464b0f1e/CAM4-7-6124-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/629d/6308051/cf3c1dbbd47e/CAM4-7-6124-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/629d/6308051/c99c464b0f1e/CAM4-7-6124-g002.jpg

相似文献

[1]
Lactate dehydrogenase A: A key player in carcinogenesis and potential target in cancer therapy.

Cancer Med. 2018-11-6

[2]
Structures of lactate dehydrogenase A (LDHA) in apo, ternary and inhibitor-bound forms.

Acta Crystallogr D Biol Crystallogr. 2015-2

[3]
Double genetic disruption of lactate dehydrogenases A and B is required to ablate the "Warburg effect" restricting tumor growth to oxidative metabolism.

J Biol Chem. 2018-8-29

[4]
Structural basis of lactate dehydrogenase A-gossypol complex.

Biochem Biophys Res Commun. 2024-11-12

[5]
FOXM1 promotes the warburg effect and pancreatic cancer progression via transactivation of LDHA expression.

Clin Cancer Res. 2014-5-15

[6]
Unappreciated Role of LDHA and LDHB to Control Apoptosis and Autophagy in Tumor Cells.

Int J Mol Sci. 2019-4-27

[7]
Stable shRNA Silencing of Lactate Dehydrogenase A (LDHA) in Human MDA-MB-231 Breast Cancer Cells Fails to Alter Lactic Acid Production, Glycolytic Activity, ATP or Survival.

Anticancer Res. 2017-3

[8]
Role of LDH in tumor glycolysis: Regulation of LDHA by small molecules for cancer therapeutics.

Semin Cancer Biol. 2022-12

[9]
The Regulation and Function of Lactate Dehydrogenase A: Therapeutic Potential in Brain Tumor.

Brain Pathol. 2016-1

[10]
Structural and functional regulation of lactate dehydrogenase-A in cancer.

Future Med Chem. 2020-3

引用本文的文献

[1]
Therapeutic Strategies Targeting Aerobic Glycolysis in Cancer and Dynamic Monitoring of Associated Metabolites.

Cells. 2025-8-19

[2]
Lactylation: a novel driver of drug resistance in the tumor microenvironment.

Cancer Drug Resist. 2025-8-4

[3]
Gold(III) Complexes with Aromatic Cyano-Substituted Bisdithiolate Ligands as Potential Anticancer and Antimicrobial Agents.

Molecules. 2025-8-4

[4]
The Evaluation of Blood Prooxidant-Antioxidant Balance Indicators and Cortisol Pre- and Post-Surgery in Patients with Benign Parotid Gland Tumors: A Preliminary Study.

J Clin Med. 2025-8-1

[5]
Dynamic serum lactate dehydrogenase monitoring during the acute phase and association with in-hospital all-cause mortality risk in large vessel occlusion acute ischemic stroke patients.

Eur J Med Res. 2025-8-13

[6]
Metabolic checkpoints in immune cell reprogramming: rewiring immunometabolism for cancer therapy.

Mol Cancer. 2025-8-2

[7]
Integrative spatial and single-cell transcriptomics elucidate programmed cell death-driven tumor microenvironment dynamics in hepatocellular carcinoma.

Front Immunol. 2025-7-16

[8]
Clinical application prospects of traditional Chinese medicine as adjuvant therapy for metabolic reprogramming in colorectal cancer.

Front Immunol. 2025-7-15

[9]
Flipping the Target: Evaluating Natural LDHA Inhibitors for Selective LDHB Modulation.

Molecules. 2025-7-10

[10]
HBV DNA integration gene CCDC91 is oncogenic and a potential therapeutic target for hepatocellular carcinoma.

Commun Biol. 2025-7-20

本文引用的文献

[1]
Increased Lactate in Gastric Cancer Tumor-Infiltrating Lymphocytes Is Related to Impaired T Cell Function Due to miR-34a Deregulated Lactate Dehydrogenase A.

Cell Physiol Biochem. 2018

[2]
MiR-323a-3p suppressed the glycolysis of osteosarcoma via targeting LDHA.

Hum Cell. 2018-8-7

[3]
miR‑199a‑3p/Sp1/LDHA axis controls aerobic glycolysis in testicular tumor cells.

Int J Mol Med. 2018-7-12

[4]
LDHA in Neuroblastoma Is Associated with Poor Outcome and Its Depletion Decreases Neuroblastoma Growth Independent of Aerobic Glycolysis.

Clin Cancer Res. 2018-6-20

[5]
Immunosuppressive Role of Myeloid-Derived Suppressor Cells and Therapeutic Targeting in Lung Cancer.

J Immunol Res. 2018-3-25

[6]
LDHA is a direct target of miR-30d-5p and contributes to aggressive progression of gallbladder carcinoma.

Mol Carcinog. 2018-3-23

[7]
miR-142-3p inhibits aerobic glycolysis and cell proliferation in hepatocellular carcinoma via targeting LDHA.

Biochem Biophys Res Commun. 2018-2-12

[8]
miR-449a Suppresses LDHA-Mediated Glycolysis to Enhance the Sensitivity of Non-Small Cell Lung Cancer Cells to Ionizing Radiation.

Oncol Res. 2017-8-11

[9]
Tumor LDH-A expression and serum LDH status are two metabolic predictors for triple negative breast cancer brain metastasis.

Sci Rep. 2017-7-20

[10]
Adenylate kinase hCINAP determines self-renewal of colorectal cancer stem cells by facilitating LDHA phosphorylation.

Nat Commun. 2017-5-18

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