ArticleJCI insight2022
The HIF-prolyl hydroxylases have distinct and nonredundant roles in colitis-associated cancer.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 7 citations in OpenAlex.
- SKA3-mediated hypoxia tolerance and metabolic reprogramming promote liver metastasis in lung adenocarcinoma.Cell death & disease · 2025Article
- Tumor Exosomal HIF2A Induce Peritumoral M2 Macrophages Accumulation to Facilitate Intestinal Invasion in Colorectal Cancer.Theranostics · 2025Article
- Natural compounds modulate the mechanism of action of tumour-associated macrophages against colorectal cancer: a review.Journal of cancer research and clinical oncology · 2024Review
- Hypoxia-Induced Signaling in Gut and Liver Pathobiology.Annual review of pathology · 2024Review
- Hypoxia inducible factor prolyl hydroxylases in inflammatory bowel disease.Frontiers in pharmacology · 2023Review
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Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Colitis-associated colorectal cancer (CAC) is a severe complication of inflammatory bowel disease (IBD). HIF-prolyl hydroxylases (PHD1, PHD2, and PHD3) control cellular adaptation to hypoxia and are considered promising therapeutic targets in IBD. However, their relevance in the pathogenesis of CAC remains elusive. We induced CAC in Phd1-/-, Phd2+/-, Phd3-/-, and WT mice with azoxymethane (AOM) and dextran sodium sulfate (DSS). Phd1-/- mice were protected against chronic colitis and displayed diminished CAC growth compared with WT mice. In Phd3-/- mice, colitis activity and CAC growth remained unaltered. In Phd2+/- mice, colitis activity was unaffected, but CAC growth was aggravated. Mechanistically, Phd2 deficiency (i) increased the number of tumor-associated macrophages in AOM/DSS-induced tumors, (ii) promoted the expression of EGFR ligand epiregulin in macrophages, and (iii) augmented the signal transducer and activator of transcription 3 and extracellular signal-regulated kinase 1/2 signaling, which at least in part contributed to aggravated tumor cell proliferation in colitis-associated tumors. Consistently, Phd2 deficiency in hematopoietic (Vav:Cre-Phd2fl/fl) but not in intestinal epithelial cells (Villin:Cre-Phd2fl/fl) increased CAC growth. In conclusion, the 3 different PHD isoenzymes have distinct and nonredundant effects, promoting (PHD1), diminishing (PHD2), or neutral (PHD3), on CAC growth.
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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 OpenQuestion graph.