ArticleCell reports2017
The mTOR and PP2A Pathways Regulate PHD2 Phosphorylation to Fine-Tune HIF1α Levels and Colorectal Cancer Cell Survival under Hypoxia.
Article in Cell reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed, 119 citations in OpenAlex.
- Article
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- Spatiotemporal dynamics of tumor-associated neutrophils: bridging the gap between cancer progression and immunotherapy.Molecular cancer · 2026Review
- Kuanxiong aerosol protects against coronary microvascular dysfunction through improving angiogenesis via HIF-1α-ITGAX axis.Frontiers in pharmacology · 2026Article
- Modulation of the tumor microenvironment by the ubiquitin-proteasome system in colorectal cancer.Journal of translational medicine · 2025Review
- Increased nuclear expression of DNA damage inducible transcript 4 can serve as a potential prognostic biomarker in patients with gliomas: a study based on data mining and experimental tools.Discover oncology · 2025Article
- LB-100 Enhances Drugs Efficacy Through Inhibition of P-Glycoprotein Expression in Multidrug-Resistant Glioblastoma and Non-Small Cell Lung Carcinoma Cellular Models.Pharmaceutics · 2025Article
- Protein serine/threonine phosphatases in tumor microenvironment: a vital player and a promising therapeutic target.Theranostics · 2025Review
- Gut microbiota interplay with autophagy-EMT dynamics in colorectal cancer.Frontiers in cell and developmental biology · 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
- Brain Specific RagA Overexpression Triggers Depressive-Like Behaviors in Mice via Activating ADORA2A Signaling Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Etrinabdione (VCE-004.8), a B55α activator, promotes angiogenesis and arteriogenesis in critical limb ischemia.Journal of translational medicine · 2024Article
- PP2Ac Regulates Autophagy via Mediating mTORC1 and ULK1 During Osteoclastogenesis in the Subchondral Bone of Osteoarthritis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Role of Protein Phosphatases in Tumor Angiogenesis: Assessing PP1, PP2A, PP2B and PTPs Activity.International journal of molecular sciences · 2024Review
- Novel hypoxia- and lactate metabolism-related molecular subtyping and prognostic signature for colorectal cancer.Journal of translational medicine · 2024Article
- Saturated fatty acids stimulate cytokine production in tanycytes via the PP2Ac-dependent signaling pathway.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
- Nuclear overexpression of DNA damage-inducible transcript 4 (DDIT4) is associated with aggressive tumor behavior in patients with pancreatic tumors.Scientific reports · 2023Article
- Astragaloside IV restrains pyroptosis and fibrotic development of pulmonary artery smooth muscle cells to ameliorate pulmonary artery hypertension through the PHD2/HIF1α signaling pathway.BMC pulmonary medicine · 2023Article
- The SGLT2 inhibitor canagliflozin suppresses growth and enhances prostate cancer response to radiotherapy.Communications biology · 2023Article
- Two-level Bayesian interaction analysis for survival data incorporating pathway information.Biometrics · 2023Article
21 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 7 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oxygen-dependent HIF1α hydroxylation and degradation are strictly controlled by PHD2. In hypoxia, HIF1α partly escapes degradation because of low oxygen availability. Here, we show that PHD2 is phosphorylated on serine 125 (S125) by the mechanistic target of rapamycin (mTOR) downstream kinase P70S6K and that this phosphorylation increases its ability to degrade HIF1α. mTOR blockade in hypoxia by REDD1 restrains P70S6K and unleashes PP2A phosphatase activity. Through its regulatory subunit B55α, PP2A directly dephosphorylates PHD2 on S125, resulting in a further reduction of PHD2 activity that ultimately boosts HIF1α accumulation. These events promote autophagy-mediated cell survival in colorectal cancer (CRC) cells. B55α knockdown blocks neoplastic growth of CRC cells in vitro and in vivo in a PHD2-dependent manner. In patients, CRC tissue expresses higher levels of REDD1, B55α, and HIF1α but has lower phospho-S125 PHD2 compared with a healthy colon. Our data disclose a mechanism of PHD2 regulation that involves the mTOR and PP2A pathways and controls tumor growth.
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