ArticleOncotarget2017
Hypoxia-inducible factor prolyl hydroxylase 2 (PHD2) is a direct regulator of epidermal growth factor receptor (EGFR) signaling in breast cancer.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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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.
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Who cites it
24 citing papers in PubMed, 39 citations in OpenAlex.
- Oncometabolite 2-hydroxyglutarate destabilizes CDH1 to regulate quiescence and enhance chemotherapy sensitivity.Cell communication and signaling : CCS · 2026Article
- Review
- PHD-2/HIF-1α axis mediates doxorubicin-induced angiogenesis in SH-SY5Y neuroblastoma microenvironment: a potential survival mechanism.Scientific reports · 2025Article
- Advances in bioengineered CAR T/NK cell therapy for glioblastoma: Overcoming immunosuppression and nanotechnology-based strategies for enhanced CAR T/NK cell therapy.Bioengineering & translational medicine · 2025Review
- Non-canonical Function of Prolyl Hydroxylase Domain 2 in Breast Cancer Cell Growth and Progression: Role of Peptidyl-prolyl Cis-trans Isomerase NIMA-interacting 1.Journal of cancer prevention · 2024Article
- Crosslinking-mediated Interactome Analysis Identified PHD2-HIF1α Interaction Hotspots and the Role of PHD2 in Regulating Protein Neddylation.bioRxiv : the preprint server for biology · 2024Article
- Prolyl hydroxylase domain enzyme PHD2 inhibits proliferation and metabolism in non-small cell lung cancer cells in HIF-dependent and HIF-independent manners.Frontiers in oncology · 2024Article
- Proline hydroxylase 2 (PHD2) promotes brown adipose thermogenesis by enhancing the hydroxylation of UCP1.Molecular metabolism · 2023Article
- The multifaceted role of EGLN family prolyl hydroxylases in cancer: going beyond HIF regulation.Oncogene · 2022Review
- A Novel PHD2/VHL-mediated Regulation of YAP1 Contributes to VEGF Expression and Angiogenesis.Cancer research communications · 2022Article
- AMP-activated protein kinase α1 phosphorylates PHD2 to maintain systemic iron homeostasis.Clinical and translational medicine · 2022Article
- Liposomal PHD2 Inhibitors and the Enhanced Efficacy in Stabilizing HIF-1α.Nanomaterials (Basel, Switzerland) · 2022Article
- HIF-Prolyl Hydroxylase Domain Proteins (PHDs) in Cancer-Potential Targets for Anti-Tumor Therapy?Cancers · 2021Review
- HIF-1α, TWIST-1 and ITGB-1, associated with Tumor Stiffness, as Novel Predictive Markers for the Pathological Response to Neoadjuvant Chemotherapy in Breast Cancer.Cancer management and research · 2020Article
- The Mammary Tumor Microenvironment.Advances in experimental medicine and biology · 2020Article
- Cellular and Extracellular Components in Tumor Microenvironment and Their Application in Early Diagnosis of Cancers.Analytical cellular pathology (Amsterdam) · 2020Review
- Signal Transduction Pathways in Breast Cancer: The Important Role of PI3K/Akt/mTOR.Journal of oncology · 2020Review
- Role of hypoxia in cancer therapy by regulating the tumor microenvironment.Molecular cancer · 2019Review
- PHD3 Acts as Tumor Suppressor in Mouse Osteosarcoma and Influences Tumor Vascularization via PDGF-C Signaling.Cancers · 2018Article
- Hypoxia-inducible factor 1-alpha expression correlates with response to neoadjuvant chemotherapy in women with breast cancer.Medicine · 2018Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Clinical studies in breast cancer suggest important associations between intratumoral hypoxia, the upregulation of epidermal growth factor receptor (EGFR or HER1), hypoxia-inducible factor 1α (HIF-1α), and reduced patient survival. However, direct molecular links between EGFR and the hypoxia signaling system are not yet established. Since the oxygen sensor hypoxia-inducible factor prolyl hydroxylase 2 (PHD2) is considered to be the main HIF-1α regulator, we hypothesized that PHD2 and EGFR may be interconnected at the molecular level. By analyzing samples from 313 breast cancer patients, we found that EGFR is a first clinicopathological parameter positively correlating with PHD2. Mechanistically, we identified PHD2 as a direct binding partner of EGFR and show that PHD2 regulates EGFR stability as well as its subsequent signaling in breast carcinoma cells. Overall, we introduce for the first time the direct crosstalk between the oxygen sensor PHD2 and EGFR-mediated tumorigenesis in breast cancer.
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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 OpenQuestion graph.