ArticleCells2022
Bone Marrow Macrophages Induce Inflammation by Efferocytosis of Apoptotic Prostate Cancer Cells via HIF-1α Stabilization.
Article in Cells, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 14 citations in OpenAlex.
- Gas6 restores microglial efferocytosis and limits neuroinflammation in neonatal hypoxic-ischemic encephalopathy by activating MerTK and the PI3K-Rac1 pathway.Cell communication and signaling : CCS · 2026Article
- PEAK1 promotes prostate cancer progression and docetaxel resistance by mediating the polarization of tumor-associated macrophages.European journal of medical research · 2026Article
- Engineering Efferocytosis for Bone Regeneration.Macromolecular bioscience · 2025Review
- Correlation between KAT6A and PD-L1 expression and role of KAT6A in colorectal cancer.World journal of gastrointestinal oncology · 2025Article
- Therapeutic targeting of myeloid cells in liver fibrosis: Mechanisms and clinical prospects.Animal models and experimental medicine · 2025Review
- [Dihydroartemisinin enhances doxorubicin-induced apoptosis of triple negative breast cancer cells by negatively regulating the STAT3/HIF-1α pathway].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Induction of osteoblast apoptosis stimulates macrophage efferocytosis and paradoxical bone formation.Bone research · 2024Article
- Single-cell transcriptome analysis deciphers the CD74-mediated immune evasion and tumour growth in lung squamous cell carcinoma with chronic obstructive pulmonary disease.Clinical and translational medicine · 2024Article
- The intricate interplay between ferroptosis and efferocytosis in cancer: unraveling novel insights and therapeutic opportunities.Frontiers in oncology · 2024Review
- The effects of preosteoblast-derived exosomes on macrophages and bone in mice.Journal of cellular and molecular medicine · 2024Article
- Tumor-specific activation of folate receptor beta enables reprogramming of immune cells in the tumor microenvironment.Frontiers in immunology · 2024Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The 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 (BM) macrophages undergoing efferocytosis of apoptotic prostate cancer cells revealed a significant enrichment in their cellular response to hypoxia. Here, we show that BM macrophage efferocytosis increased hypoxia inducible factor-1alpha (HIF-1α) and STAT3 phosphorylation (p-STAT3 at Tyr705) under normoxic conditions, while inhibitors of p-STAT3 reduced HIF-1α. Efferocytosis promoted HIF-1α stabilization, reduced its ubiquitination, and induced HIF-1α and p-STAT3 nuclear translocation. HIF-1α stabilization in efferocytic BM macrophages resulted in enhanced expression of pro-inflammatory cytokine MIF, whereas BM macrophages with inactive HIF-1α reduced MIF expression upon efferocytosis. Stabilization of HIF-1α using the HIF-prolyl-hydroxylase inhibitor, Roxadustat, enhanced MIF expression in BM macrophages. Furthermore, BM 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 BM macrophages triggers p-STAT3/HIF-1α/MIF signaling to promote further inflammation in the bone tumor microenvironment where a significant number of apoptotic cancer cells are present.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.