{"doi":"10.1093/biolre/ioaf168","title":"PTEN status on gonadotropin-releasing hormone (GnRH) metabolite, GnRH-(1–5), effects in endometrial cancer cell lines migration, & transcriptomic analysis of basal cell line and tumor gene expressions","abstract":"Previous studies have shown that the metabolite of gonadotropin-releasing hormone (GnRH), GnRH-(1-5), promotes migration and invasion in endometrial cancer cell lines through a non-canonical mechanism from its parental peptide. These studies showed that GnRH-(1-5) transactivates the epidermal growth factor receptor/extracellular signal-regulated kinases (EGFR/ERK) signaling pathway through an orphan G-protein-coupled receptor, GPR101, to stimulate matrix metalloproteinase-9 (MMP-9)-mediated EGF release to augment cellular migration and invasion. However, inhibition of the EGFR/ERK signaling pathway showed an incomplete ablation of the effects of GnRH-(1-5) in these studies to suggest that alternative signaling pathways are also involved. Given the incomplete inhibition of GnRH-(1-5) effects by EGFR/ERK pathway blockade, the present study sought to investigate the potential role of transforming growth factor beta (TGF-beta) in complementing the previously observed EGF effects on cellular function. As our previous studies were conducted in Phosphatase and Tensin homolog (PTEN)-negative cell lines, we sought to elucidate the involvement of the TGF-beta signaling pathway and the role of PTEN status in mediating the cellular responses to GnRH-(1-5). The present results show that cellular migration responses to GnRH-(1-5) involve both TGF-beta and EGF signaling pathways and are differentially regulated based on PTEN status. In addition to these cell line studies, we performed differential gene expression analysis of PTEN-positive and PTEN-negative cell lines and tumors using The Cancer Genome Atlas database. Identifying markers associated with PTEN status will allow for a more precise and rapid investigation of GnRH-(1-5) signaling mechanisms in endometrial cancer pathophysiology.","journal":"Biology of Reproduction","year":2025,"id":570940,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9523,"is_data_producer":true,"deposit_databanks":{"SRA":["SRP074707"],"BioProject":["PRJNA321028"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":295313,"name":"Gauthaman Sukumar","orcid":"0000-0003-3129-4171","position":1,"is_corresponding":false},{"id":477261,"name":"Sorana Raiciulescu","orcid":"0000-0002-1227-0134","position":2,"is_corresponding":false},{"id":241309,"name":"Clifton L. Dalgard","orcid":"0000-0003-2025-8239","position":3,"is_corresponding":false},{"id":306053,"name":"Leonardo Mariño‐Ramírez","orcid":"0000-0002-5716-8512","position":4,"is_corresponding":false},{"id":1476402,"name":"T. John Wu","orcid":"0000-0002-1505-7662","position":5,"is_corresponding":false},{"id":796861,"name":"Madelaine Cho‐Clark","orcid":null,"position":0,"is_corresponding":true}],"reference_count":96,"raw_metadata":null,"created_at":"2026-07-19T02:57:11.713851Z","pmid":"40709821","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}