{"doi":"10.1101/2023.01.31.526529","title":"B3GALT6 Promotes Dormant Breast Cancer Cell Survival and Recurrence by Enabling Heparan Sulfate-Mediated FGF Signaling","abstract":"Summary Breast cancer mortality results primarily from incurable recurrent tumors seeded by dormant, therapy-refractory residual tumor cells (RTCs). Understanding the mechanisms enabling dormant RTC survival is therefore essential for improving patient outcomes. We derived a dormancy-associated RTC signature that mirrors the transcriptional response to neoadjuvant chemotherapy in patients and is enriched for extracellular matrix-related pathways. In vivo CRISPR-Cas9 screening of dormancy-associated candidate genes identified the galactosyltransferase B3GALT6 as a functional regulator of RTC fitness. B3GALT6 covalently attaches glycosaminoglycans (GAGs) to proteins to generate proteoglycans and its germline loss-of-function causes skeletal dysplasias. We determined that B3GALT6-mediated biosynthesis of the GAG heparan sulfate predicts poor patient outcomes, promotes tumor recurrence by enhancing dormant RTC survival in multiple contexts, and does so via a B3GALT6-heparan sulfate/HS6ST1-heparan 6- O -sulfation/FGF1-FGFR2 signaling axis. These findings identify a role for B3GALT6 in cancer and suggest targeting FGF signaling as a novel approach to preventing recurrence by eradicating dormant RTCs.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":398402,"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":0.9555,"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":80919,"name":"Michelle Lu","orcid":"0000-0002-6828-0657","position":1,"is_corresponding":false},{"id":279898,"name":"Biswa Choudhury","orcid":null,"position":2,"is_corresponding":false},{"id":1040648,"name":"Tien-Chi Pan","orcid":"0000-0002-5380-0867","position":3,"is_corresponding":false},{"id":1040649,"name":"Dhruv K. Pant","orcid":"0009-0000-7002-6730","position":4,"is_corresponding":false},{"id":1040650,"name":"Christopher J. Sterner","orcid":"0009-0002-2499-9499","position":5,"is_corresponding":false},{"id":1040651,"name":"George K. Belka","orcid":"0000-0002-7070-106X","position":6,"is_corresponding":false},{"id":1041185,"name":"Takashi Toriumi","orcid":null,"position":7,"is_corresponding":false},{"id":823249,"name":"Brian Benz","orcid":null,"position":8,"is_corresponding":false},{"id":900554,"name":"Matías Escobar-Aguirre","orcid":"0000-0002-3787-7637","position":9,"is_corresponding":false},{"id":1040652,"name":"Francesco Elia Marino","orcid":"0000-0002-2400-8846","position":10,"is_corresponding":false},{"id":106562,"name":"Jeffrey D. Esko","orcid":"0000-0001-8322-1834","position":11,"is_corresponding":false},{"id":833663,"name":"Lewis A. Chodosh","orcid":"0000-0003-1027-8674","position":12,"is_corresponding":false},{"id":1040647,"name":"Amulya Sreekumar","orcid":"0000-0003-0462-0015","position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":null,"created_at":"2026-07-19T01:19:47.744358Z","pmid":null,"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":[]}