ArticleThe Journal of biological chemistry2017
Hypoxia-inducible factor 2α (HIF-2α) promotes colon cancer growth by potentiating Yes-associated protein 1 (YAP1) activity.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Discovery of common and rare genetic risk variants for colorectal cancer.Nature genetics · 2019Pooled it
- Therapeutic Targets for Hepatic Fibrosis Driven by Hypoxia-Mediated Hepatic Stellate Cell Activation.Biomolecules · 2026Review
- HIF2A as a prognostic and clinical therapeutic target in ovarian clear cell carcinoma.International journal of cancer · 2026Article
- Keratin 15 promotes a progenitor cell state in basal keratinocytes of skin epidermis.The Journal of cell biology · 2026Article
- Vitexin Attenuates the Growth and Glycolysis of Acute Myeloid Leukemia Cells by Suppressing the HIF-1α-Modulated YAP Pathway Under Hypoxic Conditions.The Kaohsiung journal of medical sciences · 2026Article
- Targeting HIF-2α in colorectal cancer reveals a cholesterol biosynthesis-dependent ferroptotic vulnerability.Cancer & metabolism · 2026Article
- Targeting HIF-2α in Colorectal Cancer Reveals a Cholesterol Biosynthesis-Dependent Ferroptotic Vulnerability.bioRxiv : the preprint server for biology · 2026Article
- A Boolean network model of hypoxia, mechanosensing and TGF-β signaling captures the role of phenotypic plasticity and mutations in tumor metastasis.PLoS computational biology · 2025Article
- Hippo/YAP signaling pathway in colorectal cancer: regulatory mechanisms and potential drug exploration.Frontiers in oncology · 2025Review
- Elucidating the Role of HIF-1α/YAP Signaling Pathway in Regulating Inflammation in Human Periodontal Stem Cells: An in vitro Study.Journal of inflammation research · 2025Article
- HIF-1α mediates hypertension and vascular remodeling in sleep apnea via hippo-YAP pathway activation.Molecular medicine (Cambridge, Mass.) · 2024Article
- HIF-2α-dependent induction of miR-29a restrains TNature communications · 2024Article
- Hypoxia-induced activation of NDR2 underlies brain metastases from Non-Small Cell Lung Cancer.Cell death & disease · 2023Article
- Hypoxia-induced YAP activation and focal adhesion turnover to promote cell migration in mesenchymal TNBC cells.Cancer medicine · 2023Article
- Yes-Associated Protein and Transcriptional Coactivator with PDZ-Binding Motif in Cardiovascular Diseases.International journal of molecular sciences · 2023Review
- Hypoxia signaling in human health and diseases: implications and prospects for therapeutics.Signal transduction and targeted therapy · 2022Review
- Mechanobiology of Colorectal Cancer.Cancers · 2022Review
- Self-Sustained Regulation or Self-Perpetuating Dysregulation: ROS-dependent HIF-YAP-Notch Signaling as a Double-Edged Sword on Stem Cell Physiology and Tumorigenesis.Frontiers in cell and developmental biology · 2022Review
- Long Noncoding RNA MALAT1 Promotes Laryngocarcinoma Development by Targeting miR-708-5p/BRD4 Axis to Regulate YAP1-Mediated Epithelial-Mesenchymal Transition.BioMed research international · 2022Article
- Effects of Ion-Transporting Proteins on the Digestive System Under Hypoxia.Frontiers in physiology · 2022Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 2 countries.
Funding
Abstract
Colorectal cancer (CRC) is the third-leading cause of cancer mortality in the United States and other industrialized countries. A hypoxic microenvironment is a hallmark for solid tumors. The hypoxia-induced signal transduction is transcriptionally mediated by hypoxia-inducible factor (HIF). Three major HIF isoforms, HIF-1α, HIF-2α, and HIF-3α, are present in the intestine. Our previous work demonstrates that HIF-2α is essential for CRC growth and progression. However, the mechanisms mediating cell proliferation after hypoxia or HIF-2α activation in CRC are unclear. Data mining of RNA-Seq experiments with mouse models of intestinal HIF-2α or Yes-associated protein 1 (YAP1) overexpression indicates a significant overlap of genes in these conditions. YAP1 is a transcriptional co-activator in the Hippo signaling pathway, and YAP1-induced transcriptional responses are essential in cancer cell proliferation. Here, we report that HIF-2α robustly increases YAP1 expression and activity in CRC-derived cell lines and in mouse models. The potentiation of YAP1 activity by HIF-2α was not via canonical signaling mechanisms such as Src (non-receptor tyrosine kinase), PI3K, ERK, or MAPK pathways. Moreover, we detected no direct interaction of HIF-2α with YAP1. Of note, YAP1 activation was critical for cancer cell growth under hypoxia. Our findings indicate that HIF-2α increases cancer cell growth by up-regulating YAP1 activity, suggesting that this pathway might be targeted in potential anti-cancer approaches for treating CRC patients.
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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.