Genetics of enzymatic dysfunctions in metabolic disorders and cancer

Frontiers in Oncology

Oncology

Tiffany J. Rios-Fuller¹  Mélanie Mahé¹  Andrea Karolin¹  Robert J. Schneider¹ 

[1] Department of Microbiology, Grossman NYU School of Medicine, New York, NY, United States;

关键词: inherited metabolic disorders;    enzymatic dysregulation;    cancer;    urea cycle;    glycogen storage;    lysosome storage;    fatty acid oxidation;    mitochondrial respiration;   

DOI  :  10.3389/fonc.2023.1230934

 received in 2023-05-29, accepted in 2023-07-19,  发布年份 2023

来源: Frontiers

【 摘 要 】

Inherited metabolic disorders arise from mutations in genes involved in the biogenesis, assembly, or activity of metabolic enzymes, leading to enzymatic deficiency and severe metabolic impairments. Metabolic enzymes are essential for the normal functioning of cells and are involved in the production of amino acids, fatty acids and nucleotides, which are essential for cell growth, division and survival. When the activity of metabolic enzymes is disrupted due to mutations or changes in expression levels, it can result in various metabolic disorders that have also been linked to cancer development. However, there remains much to learn regarding the relationship between the dysregulation of metabolic enzymes and metabolic adaptations in cancer cells. In this review, we explore how dysregulated metabolism due to the alteration or change of metabolic enzymes in cancer cells plays a crucial role in tumor development, progression, metastasis and drug resistance. In addition, these changes in metabolism provide cancer cells with a number of advantages, including increased proliferation, resistance to apoptosis and the ability to evade the immune system. The tumor microenvironment, genetic context, and different signaling pathways further influence this interplay between cancer and metabolism. This review aims to explore how the dysregulation of metabolic enzymes in specific pathways, including the urea cycle, glycogen storage, lysosome storage, fatty acid oxidation, and mitochondrial respiration, contributes to the development of metabolic disorders and cancer. Additionally, the review seeks to shed light on why these enzymes represent crucial potential therapeutic targets and biomarkers in various cancer types.

【 授权许可】

Unknown   
Copyright © 2023 Mahé, Rios-Fuller, Karolin and Schneider