{"doi":"10.1016/j.tranon.2023.101676","title":"G0S2 promotes antiestrogenic and pro-migratory responses in ER+ and ER- breast cancer cells","abstract":"G0/G1 switch gene 2 (G0S2) is known to inhibit lipolysis by inhibiting adipose triglyceride lipase (ATGL). In this report, we dissect the role of G0S2 in ER+ versus ER- breast cancer. Overexpression of G0S2 in ER- cells increased cell proliferation, while G0S2 overexpression in ER+ cells decreased cell proliferation. Transcriptome analysis revealed that G0S2 mediated distinct but overlapping transcriptional responses in ER- and ER+ cells. G0S2 reduced genes associated with an epithelial phenotype, especially in ER- cells, including CDH1, ELF3, STEAP4 and TACSTD2, suggesting promotion of the epithelial-mesenchymal transition (EMT). G0S2 also repressed estrogen signaling and estrogen receptor target gene signatures, especially in ER+ cells, including TFF1 and TFF3. In addition, G0S2 overexpression increased cell migration in ER- cells and increased estrogen deprivation sensitivity in ER+ cells. Interestingly, two genes downstream of ATGL in fat utilization and very important in steroid hormone biosynthesis, HMGCS1 and HMGCS2, were downregulated in G0S2 overexpressing ER+ cells. In addition, HSD17B11, a gene that converts estradiol to its less estrogenic derivative, estrone, was highly upregulated in G0S2 overexpressing ER+ cells, suggesting G0S2 overexpression has a negative effect on estradiol production and maintenance. High expression of G0S2 and HSD17B11 was associated with improved relapse-free survival in breast cancer patients while high expression of HMGSC1 was associated with poor survival. Finally, we deleted G0S2 in breast cancer-prone MMTV-PyMT mice. Our data indicates a complex role for G0S2 in breast cancer, dependent on ER status, that may be partially mediated by suppression of the estrogen signaling pathway.","journal":"Translational Oncology","year":2023,"id":351056,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9552,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":459861,"name":"Emmanuel Bikorimana","orcid":"0000-0002-1583-0969","position":1,"is_corresponding":false},{"id":727405,"name":"Raya I. Boyd","orcid":"0000-0002-7494-1220","position":2,"is_corresponding":false},{"id":727406,"name":"Doha Shokry","orcid":"0000-0003-1349-8381","position":3,"is_corresponding":false},{"id":457327,"name":"Kelly Kries","orcid":"0000-0003-2204-5827","position":4,"is_corresponding":false},{"id":1095767,"name":"Ayush Gupta","orcid":"0000-0002-1851-0856","position":5,"is_corresponding":false},{"id":1095768,"name":"Anneliese Paton","orcid":"0000-0003-3687-1935","position":6,"is_corresponding":false},{"id":519396,"name":"Zhengyang Sun","orcid":"0000-0003-1520-2687","position":7,"is_corresponding":false},{"id":459859,"name":"Zeeshan Fazal","orcid":"0000-0003-0111-7668","position":8,"is_corresponding":false},{"id":321967,"name":"Sarah J. Freemantle","orcid":null,"position":9,"is_corresponding":false},{"id":236654,"name":"Erik R. Nelson","orcid":"0000-0002-8887-1905","position":10,"is_corresponding":false},{"id":459865,"name":"Michael J. Spinella","orcid":"0000-0003-3150-3009","position":11,"is_corresponding":false},{"id":459860,"name":"Ratnakar Singh","orcid":"0000-0002-3226-3847","position":12,"is_corresponding":false},{"id":460509,"name":"Andrea Corbet","orcid":null,"position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-19T01:12:41.740237Z","pmid":"37086619","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":[]}