ArticleJournal of experimental & clinical cancer research : CR2018
HIF-2α promotes conversion to a stem cell phenotype and induces chemoresistance in breast cancer cells by activating Wnt and Notch pathways.
Article in Journal of experimental & clinical cancer research : CR, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
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Who cites it
101 citing papers in PubMed, 155 citations in OpenAlex.
- Exploring the Utility of ALDH1 as a Marker for the Cancer Stem Cell Population in OCCC Cell Lines.Cells · 2026Article
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- Modulation of breast cancer progression in high-altitude hypoxia by Tongqiaohuoxue Decoction via HIF-1α/VEGF signaling.Discover oncology · 2026Article
- ST6GAL1 promotes cancer stem-like cell-associated paclitaxel resistance through the EGFR-mTOR-SOX2/BMI1 axis in non-small cell lung cancer.Cancer drug resistance (Alhambra, Calif.) · 2026Article
- [Mechanistic research progress on radiotherapy resistance of cancer stem cells].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Review
- Aberrant Notch-signaling promotes tumor angiogenesis in esophageal squamous-cell carcinoma.Signal transduction and targeted therapy · 2025Article
- Targeting inflammation in cancer therapy: from mechanistic insights to emerging therapeutic approaches.Journal of translational medicine · 2025Review
- Role of the Wnt signaling pathway in the complex microenvironment of breast cancer and prospects for therapeutic potential (Review).International journal of oncology · 2025Review
- Multifaceted roles of OCT4 in tumor microenvironment: biology and therapeutic implications.Oncogene · 2025Review
- USP9X integrates TGF-β and hypoxia signalings to promote ovarian cancer chemoresistance via HIF-2α-maintained stemness.Cell death & disease · 2025Article
- Unraveling the triad of hypoxia, cancer cell stemness, and drug resistance.Journal of hematology & oncology · 2025Review
- Hypoxia-inducible factor 2 regulates alveolar regeneration after repetitive injury in three-dimensional cellular and in vivo models.Science translational medicine · 2025Article
- Review
- Review
- Canonical WNT/β-catenin signaling upregulates aerobic glycolysis in diverse cancer types.Molecular biology reports · 2024Review
- Cancer stem cells: advances in knowledge and implications for cancer therapy.Signal transduction and targeted therapy · 2024Review
- Notch signaling pathway in cancer: from mechanistic insights to targeted therapies.Signal transduction and targeted therapy · 2024Review
- Oxidative Stress in Breast Cancer: A Biochemical Map of Reactive Oxygen Species Production.Current issues in molecular biology · 2024Review
- Zinc Oxide Nanoparticles and Cancer Chemotherapy: Helpful Tools for Enhancing Chemo-sensitivity and Reducing Side Effects?Biological trace element research · 2024Review
- Hypoxia-Inducible Factor-Dependent and Independent Mechanisms Underlying Chemoresistance of Hypoxic Cancer Cells.Cancers · 2024Review
41 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundHypoxic tumor microenvironment and maintenance of stemness contribute to drug resistance in breast cancer. However, whether Hypoxia-inducible factor-2α (HIF-2α) in hypoxic tumor microenvironment mediates conversion to a stem cell phenotype and chemoresistance of breast tumors has not been elucidated.
methodsThe mRNA and protein expressions of HIF-1α, HIF-2α, Wnt and Notch pathway were determined using qRT-PCR and western blot. Cell viability and renew ability were assessed by MTT, Flow cytometric analysis and soft agar colony formation.
resultsIn our study, acute hypoxia (6-12 h) briefly increased HIF-1α expression, while chronic hypoxia (48 h) continuously enhanced HIF-2α expression and induced the resistance of breast cancer cells to Paclitaxel (PTX). Furthermore, HIF-2α overexpression induced a stem cell phenotype, the resistance to PTX and enhanced protein expression of stem cell markers, c-Myc, OCT4 and Nanog. Most importantly, Wnt and Notch signaling, but not including Shh, pathways were both activated by HIF-2α overexpression. Dickkopf-1 (DKK-1), a Wnt pathway inhibitor, and L685,458, an inhibitor of the Notch pathway, reversed the resistance to PTX and stem phenotype conversion induced by HIF-2α overexpression. In addition, HIF-2α overexpression enhanced tumorigenicity and resistance of xenograft tumors to PTX, increased activation of the Wnt and Notch pathways and induced a stem cell phenotype in vivo.
conclusionIn conclusion, HIF-2α promoted stem phenotype conversion and induced resistance to PTX by activating Wnt and Notch pathways.
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