| Abstrakt: |
The high incidence of cancer and the prevalence of chemoresistance are serious problems worldwide, underscoring the urgency of novel research focused on understanding the underlying mechanisms and finding new therapeutic targets. Recently, the G protein-coupled estrogen receptor (GPER) has received increasing attention, and it has been studied in various models, including physiological and pathological conditions, using appropriate pharmacological and molecular biological strategies. Numerous studies indicate that GPER plays an important role in cancer progression and resistance. This review focuses on the structure of GPER, the diversity of its ligands and GPER-activated signaling pathways, the role of GPER in cancer progression, and mechanisms of chemoresistance, with special emphasis on different cancer types and the tumor microenvironment. GPER was evidenced to exhibit conformational plasticity and different ligand binding modes. Therefore, GPER-mediated effects can be triggered by estrogens or various estrogen mimetics, including synthesized compounds, licensed drugs, or exogenous environmental compounds. We found multiple reports evidencing that GPER is differentially expressed in healthy tissues and tumors and plays a protumor role in breast, ovarian, lung, thyroid, and endometrial cancers. Additionally, there are several studies that indicate that GPER expression in cells of the tumor microenvironment may also contribute to cancer progression. Among the major mechanisms of GPER-mediated chemoresistance are the epithelial-mesenchymal transition, the overexpression of multidrug resistance pumps, and autophagy regulation. [ABSTRACT FROM AUTHOR] |
