ArticleEBioMedicine2021
Increased co-expression of PSMA2 and GLP-1 receptor in cervical cancer models in type 2 diabetes attenuated by Exendin-4: A translational case-control study.
Article in EBioMedicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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23 citing papers in PubMed, 28 citations in OpenAlex.
- Glucagon-like peptide-1: a critical link between gut microbiota dysbiosis and degenerative musculoskeletal diseases.Gut microbes · 2026Review
- Modulation of the tumor microenvironment by incretins and glucagon: Metabolic and immune mechanisms (Review).Experimental and therapeutic medicine · 2026Review
- The effects of incretins as a double-edged sword on cancer.Molecular biology reports · 2025Review
- Incretins and SGLT-2 inhibitors in diabetic patients with neuroendocrine tumors: current updates and future directions.Reviews in endocrine & metabolic disorders · 2025Review
- Liraglutide inhibits the development of colorectal cancer by regulating TGF-β/Smad3 signaling pathway and affecting epithelial-mesenchymal transition.Discover oncology · 2025Article
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- Glucagon-like peptide 1 receptor agonists and cancer risk: advancing precision medicine through mechanistic understanding and clinical evidence.Biomarker research · 2025 · on this mapReview
- Use of Glucagon-Like Peptide-1 Receptor Agonists Does Not Increase the Risk of Cancer in Patients with Type 2 Diabetes Mellitus.Diabetes & metabolism journal · 2025Article
- Differential Effects of GLP-1 Receptor Agonists on Cancer Risk in Obesity: A Nationwide Analysis of 1.1 Million Patients.Cancers · 2024Article
- Genome-Wide Association Study and Phenotype Prediction of Reproductive Traits in Large White Pigs.Animals : an open access journal from MDPI · 2024Article
- Comparative effectiveness of sodium-glucose cotransporter-2 inhibitors for new-onset gastric cancer and gastric diseases in patients with type 2 diabetes mellitus: a population-based cohort study.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2024Article
- The Potential Role of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists as a Type of Conservative Treatment of Endometrial Cancer in Women of Reproductive Age: A Review of the Literature and a Call for Study.Cureus · 2024 · on this mapReview
- From diabetes to diverse domains: the multifaceted roles of GLP-1 receptor agonists.Molecular biology reports · 2024Review
- From Diabetes to Oncology: Glucagon-like Peptide-1 (GLP-1) Receptor Agonist's Dual Role in Prostate Cancer.Cancers · 2024Review
- Role of SGLT2 Inhibitors, DPP-4 Inhibitors, and Metformin in Pancreatic Cancer Prevention.Cancers · 2024Review
- Glucagon-like peptide-1 receptor agonists in neoplastic diseases.Frontiers in endocrinology · 2024Review
- Comprehensively prognostic and immunological analyses of GLP-1 signaling-related genes in pan-cancer and validation in colorectal cancer.Frontiers in pharmacology · 2024Article
- Review
- Hypertension and hyperglycaemia are positively correlated with local invasion of early cervical cancer.Frontiers in endocrinology · 2023Article
- Tirzepatide-Friend or Foe in Diabetic Cancer Patients?Biomolecules · 2022Review
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Authors and funding
16 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundType 2 diabetes (T2D) increases the risk of many types of cancer. Dysregulation of proteasome-related protein degradation leads to tumorigenesis, while Exendin-4, a glucagon-like peptide 1 receptor (GLP-1R) agonist, possesses anti-cancer effects.
methodsWe explored the co-expression of proteasome alpha 2 subunit (PSMA2) and GLP-1R in the Cancer Genome Atlas (TCGA) database and human cervical cancer specimens, supplemented by in vivo and in vitro studies using multiple cervical cancer cell lines.
findingsPSMA2 expression was increased in 12 cancer types in TCGA database and cervical cancer specimens from patients with T2D (T2D vs non-T2D: 3.22 (95% confidence interval CI: 1.38, 5.05) vs 1.00 (0.66, 1.34) fold change, P = 0.01). psma2-shRNA decreased cell proliferation in vitro, and tumour volume and Ki67 expression in vivo. Exendin-4 decreased psma2 expression, tumour volume and Ki67 expression in vivo. There was no change in GLP-1R expression in 12 cancer types in TCGA database. However, GLP-1R expression (T2D vs non-T2D: 5.49 (3.0, 8.1) vs 1.00 (0.5, 1.5) fold change, P < 0.001) was increased and positively correlated with PSMA2 expression in T2D-related (r = 0.68) but not in non-T2D-related cervical cancer specimens. This correlation was corroborated by in vitro experiments where silencing glp-1r decreased psma2 expression. Exendin-4 attenuated phospho-p65 and -IκB expression in the NF-κB pathway.
interpretationPSMA2 and GLP-1R expression in T2D-related cervical cancer specimens was increased and positively correlated, suggesting hyperglycaemia might promote cancer growth by increasing PSMA2 expression which could be attenuated by Exendin-4.
fundingThis project was supported by Postdoctoral Fellowship Scheme, Direct Grant, Diabetes Research and Education Fund from the Chinese University of Hong Kong (CUHK).
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