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Glutathione‑degrading enzymes in the complex landscape of tumors (Review)
Tianyi Zhang1, Chongjie Yao2, Xu Zhou2
1Department of Acupuncture, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China.
Abstract:
Glutathione (GSH)‑degrading enzymes are essential for starting the first stages of GSH degradation. These enzymes include extracellular γ‑glutamyl transpeptidase (GGT) and intracellular GSH‑specific γ‑glutamylcyclotransferase 1 (ChaC1) and 2. These enzymes are essential for cellular activities, such as immune response, differentiation, proliferation, homeostasis regulation and programmed cell death. Tumor tissue frequently exhibits abnormal expression of GSH‑degrading enzymes, which has a key impact on the development and spread of malignancies. The present review summarizes gene and protein structure, catalytic activity and regulation of GSH‑degrading enzymes, their vital roles in tumor development (including regulation of oxidative and endoplasmic reticulum stress, control of programmed cell death, promotion of inflammation and tumorigenesis and modulation of drug resistance in tumor cells) and potential role as diagnostic biomarkers and therapeutic targets.
Insights
Glutathione (GSH)-degrading enzymes like GGT and ChaC1 are crucial for cell functions. Their abnormal expression in tumors impacts cancer development, offering potential as diagnostic biomarkers and therapeutic targets.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Glutathione (GSH) degradation is initiated by specific enzymes, including extracellular γ-glutamyl transpeptidase (GGT) and intracellular GSH-specific γ-glutamylcyclotransferase 1 (ChaC1) and 2.
- These enzymes are vital for fundamental cellular processes such as immune response, differentiation, proliferation, homeostasis, and programmed cell death.
Purpose of the Study:
- To review the structure, activity, and regulation of GSH-degrading enzymes.
- To explore the critical roles of these enzymes in tumor development and progression.
- To assess their potential as diagnostic biomarkers and therapeutic targets in oncology.
Main Methods:
- Literature review focusing on gene and protein structure, catalytic activity, and regulation of GSH-degrading enzymes.
- Analysis of the involvement of these enzymes in various aspects of tumor biology.
- Evaluation of their potential clinical applications.
Main Results:
- Abnormal expression of GSH-degrading enzymes is frequently observed in tumor tissues, significantly influencing malignancy development and metastasis.
- These enzymes play key roles in regulating oxidative and endoplasmic reticulum stress, controlling programmed cell death, promoting inflammation and tumorigenesis, and modulating drug resistance in cancer cells.
Conclusions:
- GSH-degrading enzymes are integral to cellular functions and are implicated in multiple facets of cancer biology.
- Their dysregulation in tumors highlights their significance in malignancy.
- These enzymes represent promising candidates for future diagnostic and therapeutic strategies in cancer treatment.
