{"doi":"10.1101/2021.01.29.428659","title":"LBH is a cancer stem cell- and metastasis-promoting oncogene essential for WNT stem cell function in breast cancer","abstract":"ABSTRACT Cancer stem cells (CSCs) initiate tumors, resist treatment, and seed lethal metastases; yet CSC-specific treatments are lacking. Aggressive, treatment-resistant triple-negative breast cancers (TNBC) exhibit WNT pathway activation and are CSC enriched. Here, we show that Limb-Bud- and-Heart (LBH), a WNT/β-catenin target required for normal mammary stem cell self-renewal, marks poor prognosis, stem-like TNBC, and is a key controller of breast cancer stemness. LBH is specifically expressed in tumor-initiating CD44 + CD24 -/low breast CSCs. LBH overexpression confers stem-like, metastatic traits on both TNBC and luminal origin, non-TNBC breast cancer cells by activating stem cell transcriptional programs. Importantly, silencing LBH potently suppresses tumor initiation and metastasis in vivo , and sensitizes TNBC cells to chemotherapy. LBH knockout in the MMTV-Wnt1 breast cancer mouse model, furthermore, revealed LBH is required for WNT-driven breast CSC expansion. Our findings identify LBH as an essential CSC driver downstream of WNT, and a new molecular target for anti-cancer stem cell therapy.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":216377,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.956,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":812277,"name":"Kilan C. Ashad‐Bishop","orcid":"0000-0001-6846-3499","position":1,"is_corresponding":false},{"id":812278,"name":"Sunhwa Hong","orcid":"0000-0001-8490-9366","position":2,"is_corresponding":false},{"id":272555,"name":"Rehana Qureshi","orcid":null,"position":3,"is_corresponding":false},{"id":425027,"name":"Megan E. Rieger","orcid":null,"position":4,"is_corresponding":false},{"id":812788,"name":"Linsey E. Lindley","orcid":null,"position":5,"is_corresponding":false},{"id":812279,"name":"Bin Wang","orcid":"0000-0002-2662-1986","position":6,"is_corresponding":false},{"id":812280,"name":"Diana J. Azzam","orcid":"0000-0002-2605-8855","position":7,"is_corresponding":false},{"id":689693,"name":"Mahsa Khanlari","orcid":"0000-0001-7983-2472","position":8,"is_corresponding":false},{"id":812789,"name":"Mehrad Nadji","orcid":null,"position":9,"is_corresponding":false},{"id":439826,"name":"Chaitanya Jain","orcid":"0000-0003-2429-0105","position":10,"is_corresponding":false},{"id":352777,"name":"Deukwoo Kwon","orcid":"0000-0001-5376-5320","position":11,"is_corresponding":false},{"id":620649,"name":"Yuguang Ban","orcid":"0000-0002-2874-0647","position":12,"is_corresponding":false},{"id":263247,"name":"Zhen Gao","orcid":"0000-0003-3461-1910","position":13,"is_corresponding":false},{"id":312602,"name":"Steven Chen","orcid":"0000-0003-3463-5824","position":14,"is_corresponding":false},{"id":356746,"name":"Andrew H. Sims","orcid":"0000-0001-9082-3665","position":15,"is_corresponding":false},{"id":269701,"name":"Susan B. Kesmodel","orcid":"0000-0003-0010-6078","position":16,"is_corresponding":false},{"id":269703,"name":"Joyce M. Slingerland","orcid":"0000-0003-1487-8554","position":17,"is_corresponding":false},{"id":574579,"name":"Karoline J. Briegel","orcid":"0000-0003-2661-509X","position":18,"is_corresponding":false},{"id":812276,"name":"Koteswara Rao Garikapati","orcid":"0000-0002-1189-3356","position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":null,"created_at":"2026-07-18T23:53:11.245932Z","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":[]}