{"doi":"10.1126/sciadv.adv8640","title":"Interaction between NF-κB and PLAC8 impairs autophagy providing a survival advantage to prostate cells transformed by cadmium","abstract":"Prostate cancer risk is influenced by various factors, including exposure to heavy metals like cadmium (Cd). The study reveals that the autophagy-regulating gene PLAC8 (placenta-specific 8) is significantly involved in Cd-induced prostate carcinogenesis, and NF-κB acts as the upstream transcriptional activator of PLAC8, which then selectively up-regulates BCL-xL, providing a survival advantage to Cd-transformed cells. NF-κB activation stabilizes PLAC8 in the cytosol, disrupting autophagy by allowing PLAC8 to colocalize with LC3B instead of LAMP1. Silencing NF-κB down-regulates PLAC8 and its survival function while inhibiting NF-κB or PLAC8, which restores autophagy and decreases tumor growth in xenograft models. In addition, targeting BCL-xL confirmed this signaling pathway. The findings suggest that sustained NF-κB activation regulates PLAC8 and highlights the NF-κB-PLAC8-BCL-xL axis as a potential target for early detection and therapies in metal-induced prostate cancer.","journal":"Science Advances","year":2025,"id":521417,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9584,"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":249224,"name":"Ashish Tyagi","orcid":"0000-0003-2909-5755","position":1,"is_corresponding":false},{"id":519122,"name":"Balaji Chandrasekaran","orcid":"0000-0001-7786-5385","position":2,"is_corresponding":false},{"id":1391768,"name":"Bhawna Tyagi","orcid":"0000-0001-9564-3612","position":3,"is_corresponding":false},{"id":1392281,"name":"Balpreet Singh","orcid":null,"position":4,"is_corresponding":false},{"id":1392282,"name":"Thulasidharan Nair Devanarayanan","orcid":null,"position":5,"is_corresponding":false},{"id":519123,"name":"Venkatesh Kolluru","orcid":"0000-0002-7318-2090","position":6,"is_corresponding":false},{"id":519125,"name":"Murali K. Ankem","orcid":"0000-0002-8098-979X","position":7,"is_corresponding":false},{"id":249226,"name":"Chendil Damodaran","orcid":"0000-0002-9902-7101","position":8,"is_corresponding":false},{"id":910566,"name":"Vaibhav Shukla","orcid":"0000-0003-4881-9894","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-19T02:49:44.558743Z","pmid":"40512859","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":[]}