ArticleJournal of cellular and molecular medicine2017
HIF-2α regulates non-canonical glutamine metabolism via activation of PI3K/mTORC2 pathway in human pancreatic ductal adenocarcinoma.
Article in Journal of cellular and molecular medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 33 citations in OpenAlex.
- GOT1 inhibits hepatocellular carcinoma progression by regulating SLC25A5-dependent mitochondrial apoptosis.Oncogene · 2026Article
- Pancreatic cancer: molecular pathogenesis and emerging therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Targeting Glutamine Metabolic Reprogramming in Pancreatic Cancer: Current Insights and Future Directions.Current cancer drug targets · 2026Review
- Abnormal metabolic networks participate in invasion and migration of tumors of the digestive system (Review).Oncology letters · 2025Review
- HypoxamiRs in pancreatic cancer: master regulators of the hypoxic tumor microenvironment.Cell biology and toxicology · 2025Review
- Review
- Mechanisms and therapeutic prospects of hypoxia-inducible factor 1-alpha in acute kidney injury: a systematic review.Frontiers in cell and developmental biology · 2025Review
- Article
- Glutamine addiction in tumor cell: oncogene regulation and clinical treatment.Cell communication and signaling : CCS · 2024Review
- The role of GOT1 in cancer metabolism.Frontiers in oncology · 2024Review
- Glutamine metabolism in tumor metastasis: Genes, mechanisms and the therapeutic targets.Heliyon · 2023Review
- Novel cancer treatment paradigm targeting hypoxia-induced factor in conjunction with current therapies to overcome resistance.Journal of experimental & clinical cancer research : CR · 2023Review
- Cellular metabolism in pancreatic cancer as a tool for prognosis and treatment (Review).International journal of oncology · 2022Review
- Loss of Heterozygosity forInternational journal of molecular sciences · 2022Article
- Semaphorin 6C Suppresses Proliferation of Pancreatic Cancer Cells via Inhibition of the AKT/GSK3/β-Catenin/Cyclin D1 Pathway.International journal of molecular sciences · 2022Article
- The role of metabolic reprogramming in pancreatic cancer chemoresistance.Frontiers in pharmacology · 2022Review
- The Role of Glutamine and Glutaminase in Pulmonary Hypertension.Frontiers in cardiovascular medicine · 2022Review
- Glutamine metabolism in cancers: Targeting the oxidative homeostasis.Frontiers in oncology · 2022Review
- Review
- Microenvironmental Factors Modulating Tumor Lipid Metabolism: Paving the Way to Better Antitumoral Therapy.Frontiers in oncology · 2021Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia-inducible factor-2α (HIF-2α) plays an important role in increasing cancer progression and distant metastasis in a variety of tumour types. We aimed to investigate its biological function and clinical significance in human pancreatic ductal adenocarcinoma (PDAC). A total of 283 paired PDAC tissues and adjacent normal tissues were collected from patients who underwent surgery or biopsy at Sun Yat-sen Memorial Hospital between February 2004 and October 2016. In this study, we noted that HIF-2α expression was significantly up-regulated in PDAC, positively associated with disease stage, lymph-node metastasis and patient survival, and identified as an independent prognostic factor of PDAC patients. We demonstrated that HIF-2α silencing could reduce proliferation, migration and invasion of PDAC cells in vitro. The similar effect on growth was demonstrated in vivo. Furthermore, we noted that knock-down of HIF-2α significantly decreased the expression of glutamate oxaloacetate transaminase 1 (GOT1). Importantly, we confirmed that the PI3K/mTORC2 pathway promoted GOT1 expression by targeting HIF-2α. Our study validated HIF-2α was an important factor in PDAC progression and poor prognosis and may promote non-canonical glutamine metabolism via activation of PI3K/mTORC2 pathway. Targeting HIF-2α represents a novel prognostic biomarker and therapeutic target for patients with PDAC.
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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.