{"doi":"10.1101/2021.09.02.458687","title":"Macrophages induce inflammation by efferocytosis of apoptotic prostate cancer cells via HIF-1α stabilization","abstract":"Abstract Clearance of apoptotic cancer cells by macrophages, known as efferocytosis, fuels the bone-metastatic growth of prostate cancer cells via pro-inflammatory and immunosuppressive processes. However, the exact molecular mechanisms remain unclear. In this study, single-cell transcriptomics of bone marrow macrophages undergoing efferocytosis of apoptotic prostate cancer cells revealed a significant enrichment of a cellular response to hypoxia. Here we show that efferocytic macrophages promote HIF-1α stabilization under normoxic conditions through interaction with phosphorylated STAT3. Inflammatory cytokine gene expression analysis of efferocytic HIF-1α-mutant macrophages revealed a reduced expression of the pro-tumorigenic Mif . Furthermore, stabilization of HIF-1α using the HIF-prolyl-hydroxylase inhibitor, Roxadustat, enhanced MIF expression in macrophages. Finally, macrophages treated with recombinant MIF protein activated NF-κB (p65) signaling and increased the expression of pro-inflammatory cytokines. Altogether, these findings suggest that the clearance of apoptotic cancer cells by tumor-associated macrophages triggers p-STAT3/HIF-1α/MIF signaling to enhance tumor-promoting inflammation in bone, suggesting this axis as a target for metastatic prostate cancer.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":226452,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9532,"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":318455,"name":"Patricia M. Schnepp","orcid":"0000-0002-9827-408X","position":1,"is_corresponding":false},{"id":400984,"name":"Dah Youn Baek","orcid":null,"position":2,"is_corresponding":false},{"id":400986,"name":"John R. Rubin","orcid":null,"position":3,"is_corresponding":false},{"id":444414,"name":"Ernestina Schipani","orcid":null,"position":4,"is_corresponding":false},{"id":253952,"name":"Evan T. Keller","orcid":"0000-0002-7592-7535","position":5,"is_corresponding":false},{"id":250817,"name":"Laurie K. McCauley","orcid":"0000-0001-9173-9123","position":6,"is_corresponding":false},{"id":399785,"name":"Hernan Roca","orcid":"0000-0003-2896-1455","position":7,"is_corresponding":false},{"id":399784,"name":"Veronica Mendoza‐Reinoso","orcid":"0000-0003-1776-4229","position":0,"is_corresponding":true}],"reference_count":105,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:54:34.185847Z","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":[]}