GLP1R Modulates Ferroptosis and Promotes Endometrial Cancer Progression: Insights from AN3CA Cell Study

Endometrial cancer (EC) ranks as the second most prevalent gynecologic malignancy globally, with approximately 189,000 new cases and 45,000 deaths annually. Previous research has shed light on the impact of the glucagon-like peptide 1 receptor (GLP1R) in cancers like colon and pancreatic cancers. Recent study aimed to investigate the role of the glucagon-like peptide 1 receptor (GLP1R) in endometrial cancer (EC) progression and the potential impact of GLP1R modulation on EC cell behavior.

The researchers observed that GLP1R was up-regulated in EC tissues compared to normal specimens and had the highest expression in AN3CA cells. They utilized various methods such as RT-qPCR, immunohistochemistry, and western blotting to detect GLP1R expression in EC. The study found that GLP1R knockdown significantly reduced cell viability, migration, and invasion, while inducing cell cycle arrest and apoptosis in AN3CA cells. Conversely, treatment with exendin-4, a GLP1R agonist, had the opposite effects, facilitating the malignant behaviors of AN3CA cells. Moreover, GLP1R was found to lower intracellular ROS levels and the expression of SLC7A11 and FTH1, but mitigate GPX4 expression in EC cells. This manipulation of GLP1R demonstrated its role in protecting EC cells from ferroptosis and accelerating EC progression.

Techniques and Functional Assays Used

The researchers utilized techniques such as quantitative reverse transcription PCR (RT-qPCR), western blotting, and immunohistochemistry to detect GLP1R expression in EC tissues and cell lines. They also conducted functional assays to assess the effects of GLP1R knockdown and agonist treatment on cell viability, cell cycle, apoptosis, migration, invasion, and ferroptosis.

Effects of GLP1R Manipulation in EC Cells

The study found that GLP1R up-regulation boosted the survival, migration, and invasion of EC cells, while also protecting the cells from ferroptotic cell death. Additionally, the study highlighted the changes in intracellular ROS levels and the expression of SLC7A11, FTH1, and GPX4 following GLP1R manipulation, shedding light on the underlying molecular mechanisms.

Oncogenic Role of GLP1R in EC Cells

The findings of the study indicated that GLP1R may play an oncogenic role in EC cells, influencing their proliferative, migratory, and invasive capacities. Moreover, it was found to confer protection against ferroptosis in EC cells. The study's results provide valuable insights into the function of GLP1R in EC and may have implications for the development of targeted therapeutic strategies against EC.

Implications as a Therapeutic Target

In summary, this study elucidates the role of GLP1R in EC progression, demonstrating its potential as a therapeutic target for the treatment of endometrial cancer. The detailed characterization of the effects of GLP1R manipulation on EC cell behavior and the underlying molecular mechanisms provides valuable insights into the potential therapeutic strategies for EC.

Key Points

- The study aimed to investigate the role of the glucagon-like peptide 1 receptor (GLP1R) in endometrial cancer (EC) progression and the potential impact of GLP1R modulation on EC cell behavior.

- GLP1R was found to be up-regulated in EC tissues compared to normal specimens, with the highest expression in AN3CA cells, and various methods such as RT-qPCR, immunohistochemistry, and western blotting were used to detect GLP1R expression in EC.

- GLP1R knockdown significantly reduced cell viability, migration, and invasion, while inducing cell cycle arrest and apoptosis in AN3CA cells, and treatment with exendin-4, a GLP1R agonist, had opposite effects, facilitating the malignant behaviors of AN3CA cells.

- GLP1R was found to lower intracellular ROS levels and the expression of SLC7A11 and FTH1, but mitigate GPX4 expression in EC cells, demonstrating its role in protecting EC cells from ferroptosis and accelerating EC progression.

- The study found that GLP1R up-regulation boosted the survival, migration, and invasion of EC cells, while also protecting the cells from ferroptotic cell death, shedding light on the underlying molecular mechanisms.

- The findings of the study indicated that GLP1R may play an oncogenic role in EC cells, influencing their proliferative, migratory, and invasive capacities, and conferring protection against ferroptosis. The study provides valuable insights into the function of GLP1R in EC and its potential as a therapeutic target for the treatment of endometrial cancer.

Reference -

Wu Li, Wen Lyu, Songjun Liu, Fan Ruan & Xinmei Zhang (2024) GLP1R boosts survival, migration and invasion of endometrial cancer cells and protects against ferroptotic cell death, Journal of Obstetrics and Gynaecology, 44:1, 2301324, DOI: 10.1080/01443615.2023.2301324