{"doi":"10.1016/j.isci.2020.101855","title":"Role of SPTSSB-Regulated de Novo Sphingolipid Synthesis in Prostate Cancer Depends on Androgen Receptor Signaling","abstract":"Anti-androgens are a common therapy in prostate cancer (PCa) targeting androgen receptor (AR) signaling. However, these therapies fail due to selection of highly aggressive AR-negative cancer cells that have no therapeutic options available. We demonstrate that elevating endogenous ceramide levels with administration of exogenous ceramide nanoliposomes (CNLs) was efficacious in AR-negative cell lines with limited efficacy in AR-positive cells. This effect is mediated through reduced de novo sphingolipid synthesis in AR-positive cells. We show that anti-androgens elevate de novo generation of sphingolipids via SPTSSB, a rate-limiting mediator of sphingolipid generation. Moreover, pharmacological inhibition of AR increases the efficacy of CNL in AR-positive cells through de novo synthesis, while SPTSSB knockdown limited CNL's efficacy in AR-negative cells. Alluding to clinical relevance, SPTSSB is upregulated in patients with advanced PCa after anti-androgens treatment. These findings emphasize the relevance of AR regulation upon sphingolipid metabolism and the potential of CNL as a PCa therapeutic.","journal":"iScience","year":2020,"id":105887,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9526,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":512568,"name":"Abigail Heher","orcid":null,"position":1,"is_corresponding":false},{"id":410992,"name":"Michael H. Raymond","orcid":"0000-0003-0754-9517","position":2,"is_corresponding":false},{"id":512006,"name":"Kasey Jividen","orcid":"0000-0003-1022-5038","position":3,"is_corresponding":false},{"id":410987,"name":"Jeremy J.P. Shaw","orcid":"0000-0002-7458-215X","position":4,"is_corresponding":false},{"id":512007,"name":"Bryce M. Paschal","orcid":"0000-0001-8593-0503","position":5,"is_corresponding":false},{"id":322129,"name":"Susan J. Walker","orcid":null,"position":6,"is_corresponding":false},{"id":321068,"name":"Todd E. Fox","orcid":"0000-0001-5170-3951","position":7,"is_corresponding":false},{"id":322131,"name":"Mark Kester","orcid":null,"position":8,"is_corresponding":false},{"id":410993,"name":"Pedro Costa‐Pinheiro","orcid":"0000-0002-2049-6889","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-18T23:12:23.770754Z","pmid":"33313495","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":[]}