Urinary malate dehydrogenase 2 is a new biomarker for early detection of non‐small‐cell lung cancer

Tian, Pengfei; Chen, Zhipeng; Yue, Dongsheng; Liu, Cuicui; Li, Chenguang; Chen, Chen; Zhang, Hua; Liu, Hailin; Zhang, Zhen Fa; Chen, Liang; Zhang, Bin; Wang, Changli

doi:10.1111/cas.14845

Cited by 24 publications

(15 citation statements)

References 36 publications

(62 reference statements)

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“…The upregulation of MDH2 increase energy metabolism and the deficiency of MDH2 reduces the production of ATP and the augment of ROS. MDH2 is highly expressed in many types of cancers, MDH2 concentration was higher in early-stage NSCLC patients compared with that in controls, therefore, MDH2 can be a potential biomarker for early detection of NSCLC 151 .…”

Section: Mitochondrial Function In Cancer Cell Metabolismmentioning

confidence: 97%

An Overview: The Diversified Role of Mitochondria in Cancer Metabolism

Liu¹,

Sun²,

Guo³

et al. 2023

Int. J. Biol. Sci.

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Mitochondria are intracellular organelles involved in energy production, cell metabolism and cell signaling. They are essential not only in the process of ATP synthesis, lipid metabolism and nucleic acid metabolism, but also in tumor development and metastasis. Mutations in mtDNA are commonly found in cancer cells to promote the rewiring of bioenergetics and biosynthesis, various metabolites especially oncometabolites in mitochondria regulate tumor metabolism and progression. And mutation of enzymes in the TCA cycle leads to the unusual accumulation of certain metabolites and oncometabolites. Mitochondria have been demonstrated as the target for cancer treatment. Cancer cells rely on two main energy resources: oxidative phosphorylation (OXPHOS) and glycolysis. By manipulating OXPHOS genes or adjusting the metabolites production in mitochondria, tumor growth can be restrained. For example, enhanced complex I activity increases NAD + /NADH to prevent metastasis and progression of cancers. In this review, we discussed mitochondrial function in cancer cell metabolism and specially explored the unique role of mitochondria in cancer stem cells and the tumor microenvironment. Targeting the OXPHOS pathway and mitochondria-related metabolism emerging as a potential therapeutic strategy for various cancers.

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Section: Mitochondrial Function In Cancer Cell Metabolismmentioning

confidence: 97%

An Overview: The Diversified Role of Mitochondria in Cancer Metabolism

Liu¹,

Sun²,

Guo³

et al. 2023

Int. J. Biol. Sci.

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“…Malate dehydrogenase (MDH) catalyzes the reversible interconversion of malate and oxaloacetate and their transport [ 465 ], and it has unique pharmacological selective and specificity properties and can be used as the potential antiparasitic target for drug development [ 466 ]. For example, urine malate dehydrogenase 2 can be used as a biomarker for the early detection of non-small-cell lung cancer [ 467 ].…”

Section: Reagents and Drugs Targeting Mitochondria And Epigenetics Fo...mentioning

confidence: 99%

An Epigenetic Role of Mitochondria in Cancer

Liu

Chen

Wang

et al. 2022

Cells

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Mitochondria are not only the main energy supplier but are also the cell metabolic center regulating multiple key metaborates that play pivotal roles in epigenetics regulation. These metabolites include acetyl-CoA, α-ketoglutarate (α-KG), S-adenosyl methionine (SAM), NAD+, and O-linked beta-N-acetylglucosamine (O-GlcNAc), which are the main substrates for DNA methylation and histone post-translation modifications, essential for gene transcriptional regulation and cell fate determination. Tumorigenesis is attributed to many factors, including gene mutations and tumor microenvironment. Mitochondria and epigenetics play essential roles in tumor initiation, evolution, metastasis, and recurrence. Targeting mitochondrial metabolism and epigenetics are promising therapeutic strategies for tumor treatment. In this review, we summarize the roles of mitochondria in key metabolites required for epigenetics modification and in cell fate regulation and discuss the current strategy in cancer therapies via targeting epigenetic modifiers and related enzymes in metabolic regulation. This review is an important contribution to the understanding of the current metabolic-epigenetic-tumorigenesis concept.

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“…This model of regulation of the enzyme activity of MDH2 also suggests that higher amounts of enzyme in the mitochondria will accelerate the forward reaction (in the direction of NADH) and will support the existence of the “ β -oxidation shuttle” in cancer cells. Recently, Ma et al found the level of urinary protein MDH2 to be higher in patients with non-small-cell lung cancer (NSCLC), compared to the same parameter in the healthy population [ 213 ]. MDH2 expression levels were also higher in lung cancer tissues than in normal tissues.…”

Section: Definition Of the “ β -Oxidation Shuttle”mentioning

confidence: 99%

A “Weird” Mitochondrial Fatty Acid Oxidation as a Metabolic “Secret” of Cancer

Zhelev

Aoki

Lazarova

et al. 2022

Oxidative Medicine and Cellular Longevity

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Cancer metabolism is an extensively studied field since the discovery of the Warburg effect about 100 years ago and continues to be increasingly intriguing and enigmatic so far. It has become clear that glycolysis is not the only abnormally activated metabolic pathway in the cancer cells, but the same is true for the fatty acid synthesis (FAS) and mevalonate pathway. In the last decade, a lot of data have been accumulated on the pronounced mitochondrial fatty acid oxidation (mFAO) in many types of cancer cells. In this article, we discuss how mFAO can escape normal regulation under certain conditions and be overactivated. Such abnormal activation of mitochondrial β-oxidation can also be combined with mutations in certain enzymes of the Krebs cycle that are common in cancer. If overactivated β-oxidation is combined with other common cancer conditions, such as dysfunctions in the electron transport complexes, and/or hypoxia, this may alter the redox state of the mitochondrial matrix. We propose the idea that the altered mitochondrial redox state and/or inhibited Krebs cycle at certain segments may link mitochondrial β-oxidation to the citrate-malate shuttle instead to the Krebs cycle. We call this abnormal metabolic condition “β-oxidation shuttle”. It is unconventional mFAO, a separate metabolic pathway, unexplored so far as a source of energy, as well as a source of cataplerosis, leading to biomass accumulation, accelerated oxygen consumption, and ultimately a source of proliferation. It is inefficient as an energy source and must consume significantly more oxygen per mole of ATP produced when combined with acetyl-CoA consuming pathways, such as the FAS and mevalonate pathway.

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Urinary malate dehydrogenase 2 is a new biomarker for early detection of non‐small‐cell lung cancer

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 24 publications

References 36 publications

An Overview: The Diversified Role of Mitochondria in Cancer Metabolism

An Overview: The Diversified Role of Mitochondria in Cancer Metabolism

An Epigenetic Role of Mitochondria in Cancer

A “Weird” Mitochondrial Fatty Acid Oxidation as a Metabolic “Secret” of Cancer

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