{"doi":"10.1371/journal.pone.0256238","title":"The calcium-binding protein S100B reduces IL6 production in malignant melanoma via inhibition of RSK cellular signaling","abstract":"S100B is frequently elevated in malignant melanoma. A regulatory mechanism was uncovered here in which elevated S100B lowers mRNA and secreted protein levels of interleukin-6 (IL6) and inhibits an autocrine loop whereby IL6 activates STAT3 signaling. Our results showed that S100B affects IL6 expression transcriptionally. S100B was shown to form a calcium-dependent protein complex with the p90 ribosomal S6 kinase (RSK), which in turn sequesters RSK into the cytoplasm. Consistently, S100B inhibition was found to restore phosphorylation of a nuclear located RSK substrate, CREB, which is a potent transcription factor for IL6 expression. Thus, elevated S100B reduces IL6-STAT3 signaling via RSK signaling pathway in malignant melanoma. Indeed, the elevated S100B levels in malignant melanoma cell lines correspond to low levels of IL6 and p-STAT3.","journal":"PLoS ONE","year":2021,"id":205052,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9544,"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":422163,"name":"Alexander R. Terry","orcid":"0000-0003-4731-8537","position":1,"is_corresponding":false},{"id":788428,"name":"Adam D. Pierce","orcid":null,"position":2,"is_corresponding":false},{"id":787954,"name":"Michael C. Cavalier","orcid":"0000-0001-7336-1219","position":3,"is_corresponding":false},{"id":501954,"name":"Catherine Blaha","orcid":null,"position":4,"is_corresponding":false},{"id":472249,"name":"Kaylin A. Adipietro","orcid":null,"position":5,"is_corresponding":false},{"id":421312,"name":"Paul T. Wilder","orcid":null,"position":6,"is_corresponding":false},{"id":379328,"name":"David J. Weber","orcid":"0000-0002-8824-1110","position":7,"is_corresponding":false},{"id":259748,"name":"Nissim Hay","orcid":"0000-0002-6245-3000","position":8,"is_corresponding":false},{"id":787953,"name":"Milad J. Alasady","orcid":"0000-0002-3978-1997","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-18T23:51:30.197308Z","pmid":"34411141","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":[]}