ArticleOncogene2019
Non-canonical HIF-1 stabilization contributes to intestinal tumorigenesis.
Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 37 citations in OpenAlex.
- HIF-1 attenuates high-fiber diet-mediated proliferation and stemness of colonic epithelium.Gut microbes · 2025Article
- EGLN1 (PHD2) role in tumor microenvironment: insights for therapeutic targeting.Experimental & molecular medicine · 2025Review
- Exploration of the roles of CAFs in melanoma based on single-cell transcriptomics and spatial transcriptomics.Discover oncology · 2025Article
- Review
- Impact of HIF-1α, LOX and ITGA5 Synergistic Interaction in the Tumor Microenvironment on Colorectal Cancer Prognosis.Diagnostics (Basel, Switzerland) · 2025Article
- Influence of Hypoxia on the Airway Epithelium.Physiological research · 2024Review
- A landscape of patient-derived cancer-associated fibroblast signals in endometrial cancers.American journal of cancer research · 2024Article
- Roxadustat: Do we know all the answers?Biomolecules & biomedicine · 2023Review
- Protective Effect of Qingchang Wenzhong Decoction on Colitis and Colitis-Related Carcinogenesis by Regulating Inflammation and Intestinal Fibrosis.Journal of inflammation research · 2023Article
- Signaling pathways in cancer-associated fibroblasts: recent advances and future perspectives.Cancer communications (London, England) · 2023Review
- Mapping knowledge structure and themes trends of cancer-associated fibroblasts: a text-mining study.Frontiers in molecular biosciences · 2023Article
- Pulmonary Thrombosis Promotes Tumorigenesis via Myeloid Hypoxia-Inducible Factors.Biomolecules · 2022Article
- Article
- Dihydroartemisinin ameliorates chronic nonbacterial prostatitis and epithelial cellular inflammation by blocking the E2F7/HIF1α pathway.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022Article
- Diosmetin has therapeutic efficacy in colitis regulating gut microbiota, inflammation, and oxidative stress via the circ-Sirt1/Sirt1 axis.Acta pharmacologica Sinica · 2022Article
- Hif1α and Wnt are required for posterior gene expression during Xenopus tropicalis tail regeneration.Developmental biology · 2022Article
- Stabilization but No Functional Influence of HIF-1α Expression in the Intestinal Epithelium during Salmonella Typhimurium Infection.Infection and immunity · 2022Article
- Synthetic lethality between MyD88 loss and mutations in Wnt/β-catenin pathway in intestinal tumor epithelial cells.Oncogene · 2021Article
- Wnt Signaling in the Tumor Microenvironment.Advances in experimental medicine and biology · 2021Article
- Epigenetic crosstalk between hypoxia and tumor driven by HIF regulation.Journal of experimental & clinical cancer research : CR · 2020Review
Corrections and comments
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Authors and funding
26 authors at 8 institutions in 4 countries.
Funding
Abstract
The hypoxia-inducible transcription factor HIF-1 is appreciated as a promising target for cancer therapy. However, conditional deletion of HIF-1 and HIF-1 target genes in cells of the tumor microenvironment can result in accelerated tumor growth, calling for a detailed characterization of the cellular context to fully comprehend HIF-1's role in tumorigenesis. We dissected cell type-specific functions of HIF-1 for intestinal tumorigenesis by lineage-restricted deletion of the Hif1a locus. Intestinal epithelial cell-specific Hif1a loss reduced activation of Wnt/β-catenin, tumor-specific metabolism and inflammation, significantly inhibiting tumor growth. Deletion of Hif1a in myeloid cells reduced the expression of fibroblast-activating factors in tumor-associated macrophages resulting in decreased abundance of tumor-associated fibroblasts (TAF) and robustly reduced tumor formation. Interestingly, hypoxia was detectable only sparsely and without spatial association with HIF-1α, arguing for an importance of hypoxia-independent, i.e., non-canonical, HIF-1 stabilization for intestinal tumorigenesis that has not been previously appreciated. This adds a further layer of complexity to the regulation of HIF-1 and suggests that hypoxia and HIF-1α stabilization can be uncoupled in cancer. Collectively, our data show that HIF-1 is a pivotal pro-tumorigenic factor for intestinal tumor formation, controlling key oncogenic programs in both the epithelial tumor compartment and the tumor microenvironment.
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