{"doi":"10.1371/journal.pone.0247394","title":"IL-6 promotes MYC-induced B cell lymphomagenesis independent of STAT3","abstract":"The inflammatory cytokine IL-6 is known to play a causal role in the promotion of cancer, although the underlying mechanisms remain to be completely understood. Interplay between endogenous and environmental cues determines the fate of cancer development. The Eμ-myc transgenic mouse expresses elevated levels of c-Myc in the B cell lineage and develops B cell lymphomas with associated mutations in p53 or other genes linked to apoptosis. We generated Eμ-myc mice that either lacked the IL-6 gene, or lacked the STAT3 gene specifically in B cells to determine the role of the IL-6/JAK/STAT3 pathway in tumor development. Using the Eμ-myc lymphoma mouse model, we demonstrate that IL-6 is a critical tumor promoter during early stages of B cell lymphomagenesis. IL-6 is shown to inhibit the expression of tumor suppressors, notably BIM and PTEN, and this may contribute to advancing MYC-driven B cell tumorigenesis. Several miRNAs known to target BIM and PTEN are upregulated by IL-6 and likely lead to the stable suppression of pro-apoptotic pathways early during the tumorigenic process. STAT3, a classical downstream effector of IL-6, appears dispensable for Eμ-myc driven lymphomagenesis. We conclude that the growth-promoting and anti-apoptotic mechanisms activated by IL-6 are critically involved in Eμ-myc driven tumor initiation and progression, but the B cell intrinsic expression of STAT3 is not required.","journal":"PLoS ONE","year":2021,"id":193729,"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":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9503,"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":526908,"name":"Jinyu Li","orcid":"0000-0002-8220-049X","position":1,"is_corresponding":false},{"id":762304,"name":"Velasco Cimica","orcid":"0000-0001-7489-3145","position":2,"is_corresponding":false},{"id":762811,"name":"Patricio Mena-Taboada","orcid":null,"position":3,"is_corresponding":false},{"id":762305,"name":"Ha Youn Shin","orcid":"0000-0002-8553-2107","position":4,"is_corresponding":false},{"id":624213,"name":"Stephen D’Amico","orcid":"0009-0004-6425-7822","position":5,"is_corresponding":false},{"id":245462,"name":"Nancy C. Reich","orcid":"0000-0003-4367-6097","position":6,"is_corresponding":false},{"id":624216,"name":"Oleksi Petrenko","orcid":"0000-0002-9121-8843","position":0,"is_corresponding":true}],"reference_count":81,"raw_metadata":null,"created_at":"2026-07-18T23:49:51.300073Z","pmid":"33651821","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":[]}