Significance of Malic Enzyme 1 in Cancer: A Review

Fujiwara-Tani, Rina; Nakashima, Chie; Ohmori, Hitoshi; Fujii, Kiyomu; Luo, Yi; Sasaki, Takamitsu; Ogata, Ruiko; Kuniyasu, Hiroki

doi:10.3390/cimb47020083

Open AccessReview

Significance of Malic Enzyme 1 in Cancer: A Review

by

Rina Fujiwara-Tani

^*,

Chie Nakashima

,

Hitoshi Ohmori

,

Kiyomu Fujii

,

Yi Luo

,

Takamitsu Sasaki

,

Ruiko Ogata

and

Hiroki Kuniyasu

^*

Department of Molecular Pathology, Nara Medical University School of Medicine, 840 Shijo-cho, Kashihara 634-8521, Japan

^*

Authors to whom correspondence should be addressed.

Curr. Issues Mol. Biol. 2025, 47(2), 83; https://doi.org/10.3390/cimb47020083

Submission received: 2 January 2025 / Revised: 25 January 2025 / Accepted: 28 January 2025 / Published: 29 January 2025

(This article belongs to the Special Issue New Insight: Enzymes as Targets for Drug Development, 2nd Edition)

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Abstract

Malic enzyme 1 (ME1) plays a key role in promoting malignant phenotypes in various types of cancer. ME1 promotes epithelial–mesenchymal transition (EMT) and enhances stemness via glutaminolysis, energy metabolism reprogramming from oxidative phosphorylation to glycolysis. As a result, ME1 promotes the malignant phenotypes of cancer cells and poor patient prognosis. In particular, ME1 expression is promoted in hypoxic environments associated with hypoxia-inducible factor (HIF1) α. ME1 is overexpressed in budding cells at the cancer invasive front, promoting cancer invasion and metastasis. ME1 also generates nicotinamide adenine dinucleotide (NADPH), which, together with glucose-6-phosphate dehydrogenase (G6PD) and isocitrate dehydrogenase (IDH1), expands the NADPH pool, maintaining the redox balance in cancer cells, suppressing cell death by neutralizing mitochondrial reactive oxygen species (ROS), and promoting stemness. This review summarizes the latest research insights into the mechanisms by which ME1 contributes to cancer progression. Because ME1 is involved in various aspects of cancer and promotes many of its malignant phenotypes, it is expected that ME1 will become a novel drug target in the near future.

Keywords: malic enzyme 1; cancer stem cells; energy metabolism; epithelial–mesenchymal transition; hypoxia

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MDPI and ACS Style

Fujiwara-Tani, R.; Nakashima, C.; Ohmori, H.; Fujii, K.; Luo, Y.; Sasaki, T.; Ogata, R.; Kuniyasu, H. Significance of Malic Enzyme 1 in Cancer: A Review. Curr. Issues Mol. Biol. 2025, 47, 83. https://doi.org/10.3390/cimb47020083

AMA Style

Fujiwara-Tani R, Nakashima C, Ohmori H, Fujii K, Luo Y, Sasaki T, Ogata R, Kuniyasu H. Significance of Malic Enzyme 1 in Cancer: A Review. Current Issues in Molecular Biology. 2025; 47(2):83. https://doi.org/10.3390/cimb47020083

Chicago/Turabian Style

Fujiwara-Tani, Rina, Chie Nakashima, Hitoshi Ohmori, Kiyomu Fujii, Yi Luo, Takamitsu Sasaki, Ruiko Ogata, and Hiroki Kuniyasu. 2025. "Significance of Malic Enzyme 1 in Cancer: A Review" Current Issues in Molecular Biology 47, no. 2: 83. https://doi.org/10.3390/cimb47020083

APA Style

Fujiwara-Tani, R., Nakashima, C., Ohmori, H., Fujii, K., Luo, Y., Sasaki, T., Ogata, R., & Kuniyasu, H. (2025). Significance of Malic Enzyme 1 in Cancer: A Review. Current Issues in Molecular Biology, 47(2), 83. https://doi.org/10.3390/cimb47020083

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Significance of Malic Enzyme 1 in Cancer: A Review

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