{"doi":"10.1016/j.jbc.2025.111069","title":"IGFBP-6 regulates breast cancer cell cycle progression by promoting exit out of G1","abstract":"While the contribution of the IGF-signaling axis in breast cancer is well-documented, the role of IGFBP-6 in breast carcinogenesis has not been extensively studied. In general, insulin-like growth factor binding protein-6 (IGFBP-6) sequesters insulin-like growth factor 2 (IGF-2) to attenuate activation of its cognate receptor IGF-1R. To reveal previously unknown mechanisms of breast cancer modulation by IGFBP-6 in breast cancer, proteomic analysis was performed in T47D cells after IGFBP-6 knockdown. Comparing protein expression and phosphosites after knockdown by unique siRNA sequences with a negative control and subsequent pathway analysis, a decrease in IGFBP-6 expression resulted in activation of interferon signaling pathways and a decrease in pathways involved in the G2/M cell cycle transition. A subset of the proteins identified in each cell regulatory pathway was validated by immunoblotting for specific proteins after IGFBP-6 knockdown. Cell cycle analysis showed that IGFBP-6 knockdown in Hormone Receptor Positive T47D breast cancer cells resulted in an increased number of cells in the G1 phase and a decrease in cells in G2, indicating a role for IGFBP-6 in cell cycle regulation. Knockdown of IGFBP-6 in a triple-negative breast cancer cell line, MDA-MB-231, also resulted in a decrease in Cyclin B1 accumulation, demonstrating that our observations are not cell line specific. Taken together, our results demonstrate that IGFBP-6 regulates cell cycle progression in breast cancer cells and interferon signaling in hormone-positive cells.","journal":"Journal of Biological Chemistry","year":2025,"id":549525,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9569,"is_data_producer":false,"deposit_databanks":null,"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":1444259,"name":"Shayla Hernandez","orcid":null,"position":1,"is_corresponding":false},{"id":1444260,"name":"Diana C. Bautista-Tovar","orcid":null,"position":2,"is_corresponding":false},{"id":485431,"name":"Kevin D. Houston","orcid":"0000-0002-9858-1901","position":3,"is_corresponding":false},{"id":1444258,"name":"Francisco Javier Lariz","orcid":null,"position":0,"is_corresponding":true}],"reference_count":64,"raw_metadata":null,"created_at":"2026-07-19T02:54:07.823422Z","pmid":"41419198","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":[]}