Targeting PGAM1 in cancer: An emerging therapeutic opportunity
Guan-Jun Yang1, Fan Tao2, Hai-Jing Zhong3
1State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Ningbo University, Ningbo, 315211, Zhejiang, China; Laboratory of Biochemistry and Molecular Biology, School of Marine Sciences, Ningbo University, Ningbo, 315211, China; Key Laboratory of Aquacultural Biotechnology Ministry of Education, Ningbo University, Ningbo, 315211, China.
Abstract:
Glycolysis is a preferred metabolic pattern of cancer cells. Phosphoglycerate mutase 1 (PGAM1) is a pivotal glycolytic enzyme that catalyzes the reciprocal conversion between 2-phosphoglycerate and 3-phosphoglycerate. It also stimulates anabolic pathways, generates adenosine triphosphate, and keeps redox balance under hypoxic conditions. Mounting evidence supports that PGAM1 is overexpressed in many cancers and promotes their progression. The critical roles of PGAM1 in tumorigenesis make it a promising theranostical target for cancer. The aberrant expression of PGAM1 enables it to become a potential diagnosis gene for several cancers, and its heterogeneous regulations via interacting with its different ligands increase the possibility of it as a target for cancer therapy and discovery of tens of PGAM1 inhibitors, which can provide the potential feasibility for cancer treatment. This review provides insights into structure, function, and regulation of PGAM1, summarizes its mechanism in tumorigenesis, reviews the advanced status of PGAM1 inhibitors in cancer diagnosis and treatment, and finally emphasizes PGAM1 as an appealing theranostical target for cancer.
Insights
Phosphoglycerate mutase 1 (PGAM1) is crucial for cancer cell metabolism and progression. Targeting PGAM1 offers a promising theranostic strategy for cancer diagnosis and treatment.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Glycolysis is a key metabolic pathway utilized by cancer cells.
- Phosphoglycerate mutase 1 (PGAM1) is a critical enzyme in glycolysis, supporting cancer cell survival and proliferation.
- PGAM1 is frequently overexpressed in various cancers, driving tumorigenesis.
Purpose of the Study:
- To review the structure, function, and regulation of PGAM1.
- To elucidate the mechanisms by which PGAM1 contributes to tumorigenesis.
- To summarize the current advancements in PGAM1 inhibitors for cancer diagnosis and treatment.
Main Methods:
- Literature review of scientific publications on PGAM1.
- Analysis of PGAM1's role in cancer metabolism and progression.
- Evaluation of PGAM1 inhibitors in preclinical and clinical settings.
Main Results:
- PGAM1 plays multifaceted roles in cancer, including promoting anabolism, ATP generation, and redox balance under hypoxia.
- Aberrant PGAM1 expression serves as a potential diagnostic marker for several cancers.
- Numerous PGAM1 inhibitors have been developed, demonstrating therapeutic potential.
Conclusions:
- PGAM1 is a significant driver of cancer progression and a viable theranostic target.
- Targeting PGAM1 offers a promising avenue for developing novel cancer therapies.
- Further research into PGAM1 regulation and inhibitor development is warranted.
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