ArticleProceedings of the National Academy of Sciences of the United States of America2022
Progesterone activates GPR126 to promote breast cancer development via the Gi pathway.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Bilateral breast nodules as an unusual manifestation of 17α-hydroxylase/17,20-lyase deficiency.Frontiers in endocrinology · 2025Pooled it
- Review
- Ligand-tuned extracellular domain dynamics are correlated with signaling states in an adhesion GPCR.Science advances · 2026Article
- The therapeutic potential of orphan adhesion G-protein-coupled receptors.Nature reviews. Drug discovery · 2026Review
- Characterization of ADGRG6 as a potential molecular oncotarget of pancreatic cancer.Cell death & disease · 2026Article
- Adhesion G protein-coupled receptors.Pharmacological reviews · 2026Review
- ChIP happens: from biochemical origins to the modern omics toolbox for understanding steroid hormone receptors.The Biochemical journal · 2026Review
- Regulatory roles of bioactive lipids in vascular homeostasis and remodeling.Medical review (2021) · 2026Review
- Article
- Article
- Integrating Multiple Methods to Validate Key Genes Driving the Progression of Breast Ductal Carcinoma In Situ.Current issues in molecular biology · 2025Article
- Development of an allosteric adhesion GPCR nanobody with therapeutic potential.Nature chemical biology · 2025Article
- Multimodal analysis of cell-free DNA enhances differentiation of early-stage breast cancer from benign lesions and healthy individuals.BMC biology · 2025Article
- Domain-specific N-glycosylation of the adhesion G-protein-coupled receptor ADGRG6 N-terminal fragment regulates trafficking, proteolytic processing, and signaling.Molecular biology of the cell · 2025Article
- Exogenous activation of the adhesion GPCR ADGRD1/GPR133 protects against bone loss by negatively regulating osteoclastogenesis.Science advances · 2025Article
- Tracing the Evolution of Sex Hormones and Receptor-Mediated Immune Microenvironmental Differences in Prostate and Bladder Cancers: From Embryonic Development to Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Determining the Molecular Shape of Progesterone: Insights from Laser Ablation Rotational Spectroscopy.The journal of physical chemistry letters · 2025Article
- Identification of a novel prognostic marker ADGRG6 in pancreatic adenocarcinoma: multi-omics analysis and experimental validation.Frontiers in immunology · 2025Article
- Joint Screening for Ultra-High Dimensional Multi-Omics Data.Bioengineering (Basel, Switzerland) · 2024Article
- The G protein-coupled receptor ADGRG6 maintains mouse growth plate homeostasis through IHH signaling.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2024Article
Corrections and comments
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Authors and funding
21 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
GPR126 is a member of the adhesion G protein-coupled receptors (aGPCRs) that is essential for the normal development of diverse tissues, and its mutations are implicated in various pathological processes. Here, through screening 34 steroid hormones and their derivatives for cAMP production, we found that progesterone (P4) and 17-hydroxyprogesterone (17OHP) could specifically activate GPR126 and trigger its downstream Gi signaling by binding to the ligand pocket in the seven-transmembrane domain of the C-terminal fragment of GPR126. A detailed mutagenesis screening according to a computational simulated structure model indicated that K1001ECL2 and F1012ECL2 are key residues that specifically recognize 17OHP but not progesterone. Finally, functional analysis revealed that progesterone-triggered GPR126 activation promoted cell growth in vitro and tumorigenesis in vivo, which involved Gi-SRC pathways in a triple-negative breast cancer model. Collectively, our work identified a membrane receptor for progesterone/17OHP and delineated the mechanisms by which GPR126 participated in potential tumor progression in triple-negative breast cancer, which will enrich our understanding of the functions and working mechanisms of both the aGPCR member GPR126 and the steroid hormone progesterone.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.