Malic enzymes in cancer: Regulatory mechanisms, functions, and therapeutic implications
Huan Wang,
Wanlin Cui,
Song Yue,
Xianglong Zhu,
Xiaoyan Li,
Lian He,
Mingrong Zhang,
Yan Yang,
Minjie Wei,
Huizhe Wu,
Shuo Wang
Affiliations
Huan Wang
Department of Radiotherapy, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Cancer Hospital of Dalian University of Technology, No.44 Xiaoheyan Road, Dadong District, Shenyang, 110042, Liaoning Province, PR China
Wanlin Cui
Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, 110122, Liaoning Province, PR China; Liaoning Key Laboratory of Molecular Targeted Anti-tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, 110122, Liaoning Province, PR China
Song Yue
Department of Ophthalmology, The First Hospital of China Medical University, Shenyang, Liaoning Province, PR China
Xianglong Zhu
Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, 110122, Liaoning Province, PR China; Liaoning Key Laboratory of Molecular Targeted Anti-tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, 110122, Liaoning Province, PR China
Xiaoyan Li
Department of Pathology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Cancer Hospital of Dalian University of Technology, No.44 Xiaoheyan Road, Dadong District, Shenyang, 110042, Liaoning Province, PR China
Lian He
Department of Pathology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Cancer Hospital of Dalian University of Technology, No.44 Xiaoheyan Road, Dadong District, Shenyang, 110042, Liaoning Province, PR China
Mingrong Zhang
Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, 110122, Liaoning Province, PR China; Liaoning Key Laboratory of Molecular Targeted Anti-tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, 110122, Liaoning Province, PR China
Yan Yang
Department of Gastroenterology, The Fourth Affiliated Hospital of China Medical University, No.4, Chongshan Road, Huanggu District, Shenyang, Liaoning Province, PR China
Minjie Wei
Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, 110122, Liaoning Province, PR China; Liaoning Key Laboratory of Molecular Targeted Anti-tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, 110122, Liaoning Province, PR China; Shenyang Kangwei Medical Laboratory Analysis Co. LTD, Shenyang City, Liaoning Province, PR China; Corresponding author. Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, 110122, Liaoning Province, PR China.
Huizhe Wu
Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, 110122, Liaoning Province, PR China; Liaoning Key Laboratory of Molecular Targeted Anti-tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, 110122, Liaoning Province, PR China; Corresponding author. Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, 110122, Liaoning Province, PR China.
Shuo Wang
Department of Gynecology Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Cancer Hospital of Dalian University of Technology, No.44 Xiaoheyan Road, Dadong District, Shenyang, 110042, Liaoning Province, PR China; Corresponding author.
Malic enzymes (MEs) are metabolic enzymes that catalyze the oxidation of malate to pyruvate and NAD(P)H. While researchers have well established the physiological metabolic roles of MEs in organisms, recent research has revealed a link between MEs and carcinogenesis. This review collates evidence of the molecular mechanisms by which MEs promote cancer occurrence, including transcriptional regulation, post-transcriptional regulation, post-translational protein modifications, and protein-protein interactions. Additionally, we highlight the roles of MEs in reprogramming energy metabolism, suppressing senescence, and modulating the tumor immune microenvironment. We also discuss the involvement of these enzymes in mediating tumor resistance and how the development of novel small-molecule inhibitors targeting MEs might be a good therapeutic approach. Insights through this review are expected to provide a comprehensive understanding of the intricate relationship between MEs and cancer, while facilitating future research on the potential therapeutic applications of targeting MEs in cancer management.
