ArticleOncogene2021
Direct phosphorylation and stabilization of HIF-1α by PIM1 kinase drives angiogenesis in solid tumors.
Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 41 citations in OpenAlex.
- Hypoxia-inducible factor-1a (HIF1a) as a context-dependent integrator of metabolic stress in skeletal muscle.The Journal of physiology · 2026Review
- Hypoxia-Driven Mechanisms in Ischemic Heart Failure: A Bioinformatics, Machine Learning and Bayesian Network Study.Cardiovascular toxicology · 2026Article
- Hypoxia-inducible factor-1 (HIF-1) in the molecular mechanisms of liver fibrosis: research progress on its role and therapeutic strategies.Journal of applied genetics · 2026Review
- Review
- Exploring PIM1 Kinase as a Therapeutic Target: Mechanisms and Strategies in Cancer Treatment.International journal of molecular sciences · 2026Review
- Tumor Anti-Angiogenesis Therapy and Its Influence on Immune Cell Function in the Tumor Microenvironment.Cancer medicine · 2026Review
- Review
- JAK2V617F reprograms Hypoxia Inducible Factor-1 to induce a non-canonical hypoxia regulon in myeloproliferative neoplasms.Leukemia · 2026Article
- EGLN1 (PHD2) role in tumor microenvironment: insights for therapeutic targeting.Experimental & molecular medicine · 2025Review
- HIF-1α Promotes the Confined Migration of Gastric Cancer Cells by Modulating Phosphatidylcholine Metabolism.Journal of cellular and molecular medicine · 2025Article
- The HIF axes in cancer: angiogenesis, metabolism, and immune-modulation.Trends in biochemical sciences · 2025Review
- From Hypoxia to Bone: Reprogramming the Prostate Cancer Metastatic Cascade.International journal of molecular sciences · 2025Review
- Inhibition of PIM Kinase in Tumor-Associated Macrophages Suppresses Inflammasome Activation and Sensitizes Prostate Cancer to Immunotherapy.Cancer immunology research · 2025Article
- PIM kinase inhibition counters resistance to radiotherapy and chemotherapy in human prostate cancer.Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology · 2025Article
- Roles of Post-Translational Modifications of Transcription Factors Involved in Breast Cancer Hypoxia.Molecules (Basel, Switzerland) · 2025Review
- Expression of PIM1/ASK1 Molecular Pathway Related Genes in Ischemic Cardiomyopathy.Cardiovascular & hematological disorders drug targets · 2025Article
- PIM1 instigates endothelial-to-mesenchymal transition to aggravate atherosclerosis.Theranostics · 2025Article
- Branched-chain α-ketoacids aerobically activate HIF1α signalling in vascular cells.Nature metabolism · 2024Article
- Single-cell RNA-Seq reveals the heterogeneity of fibroblasts within the tympanojugular paraganglioma microenvironment.Heliyon · 2024Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Angiogenesis is essential for the sustained growth of solid tumors. Hypoxia-inducible factor 1 (HIF-1) is a master regulator of angiogenesis and constitutive activation of HIF-1 is frequently observed in human cancers. Therefore, understanding the mechanisms governing the activation of HIF-1 is critical for successful therapeutic targeting of tumor angiogenesis. Herein, we establish a new regulatory mechanism responsible for the constitutive activation of HIF-1α in cancer, irrespective of oxygen tension. PIM1 kinase directly phosphorylates HIF-1α at threonine 455, a previously uncharacterized site within its oxygen-dependent degradation domain. This phosphorylation event disrupts the ability of prolyl hydroxylases to bind and hydroxylate HIF-1α, interrupting its canonical degradation pathway and promoting constitutive transcription of HIF-1 target genes. Moreover, phosphorylation of the analogous site in HIF-2α (S435) stabilizes the protein through the same mechanism, indicating post-translational modification within the oxygen-dependent degradation domain as a mechanism of regulating the HIF-α subunits. In vitro and in vivo models demonstrate that expression of PIM1 is sufficient to stabilize HIF-1α and HIF-2α in normoxia and stimulate angiogenesis in a HIF-1-dependent manner. CRISPR mutants of HIF-1α (Thr455D) promoted increased tumor growth, proliferation, and angiogenesis. Moreover, HIF-1α-T455D xenograft tumors were refractory to the anti-angiogenic and cytotoxic effects of PIM inhibitors. These data identify a new signaling axis responsible for hypoxia-independent activation of HIF-1 and expand our understanding of the tumorigenic role of PIM1 in solid tumors.
Indexed as
Identifiers
What OpenQuestion holds
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 OpenQuestion graph.