ArticleOncotarget2018
Hypoxia-inducible factor-2 alpha up-regulates CD70 under hypoxia and enhances anchorage-independent growth and aggressiveness in cancer cells.
Article in Oncotarget, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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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
26 citing papers in PubMed, 32 citations in OpenAlex.
- Affinity-optimized bispecific CAR-T cells targeting HLA-G and CD70 for the treatment of clear cell renal cell carcinoma.Journal for immunotherapy of cancer · 2026Article
- Repurposing Seleno-L-Methionine as a Pleiotropic Immunomodulatory Agent to Overcome TGF-β1/HIF-Driven Immune Evasion in Clear Cell Renal Cell Carcinoma: Mechanistic Insights and Translational Therapeutic Opportunities.International journal of molecular sciences · 2026Review
- Regulation of immune checkpoint molecules in cancer immune evasion and therapy.Nature reviews. Cancer · 2026Review
- CD70 drives cSCC growth by linking DNA damage response, inflammation, and tumor-stromal signaling.Cell death & disease · 2026Article
- CD70/CD27 signaling promotes the pathogenesis of multiple myeloma and represents a promising therapeutic target.Leukemia · 2026Article
- Epigenetic alterations in cancer metastasis: molecular mechanisms and implications for precision oncology.Frontiers in oncology · 2026Review
- CD70 drives cSCC growth by linking DNA damage response, inflammation, and tumor-stromal signaling.Research square · 2025Article
- PI3 K/AKT/mTOR pathway and its role in breast cancer stem cells.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Tumor heterogeneity and resistance in glioblastoma: the role of stem cells.Apoptosis : an international journal on programmed cell death · 2025Review
- Preclinical development and evaluation of nanobody-based CD70-specific CAR T cells for the treatment of acute myeloid leukemia.Cancer immunology, immunotherapy : CII · 2023Article
- Expression of soluble CD27 in extranodal natural killer/T-cell lymphoma, nasal type: potential as a biomarker for diagnosis and CD27/CD70-targeted therapy.Cancer immunology, immunotherapy : CII · 2023Article
- Hypoxia-Inducible Factor-2α Signaling in the Skeletal System.JBMR plus · 2023Review
- Molecular and immunological mechanisms of clonal evolution in multiple myeloma.Frontiers in immunology · 2023Review
- CD70-Targeted Micelles Enhance HIF2α siRNA Delivery and Inhibit Oncogenic Functions in Patient-Derived Clear Cell Renal Carcinoma Cells.Molecules (Basel, Switzerland) · 2022Article
- Hypoxia-hindered methylation of PTGIS in endometrial stromal cells accelerates endometriosis progression by inducing CD16Experimental & molecular medicine · 2022Article
- Extracellular Vesicles-A New Potential Player in the Immunology of Renal Cell Carcinoma.Journal of personalized medicine · 2022Review
- Non-cleavable hinge enhances avidity and expansion of CAR-T cells for acute myeloid leukemia.Cancer cell · 2022Article
- Hypoxia-Inducible Factor-2 Alpha Regulates the Migration of Fibroblast-like Synoviocytes via Oxidative Stress-Induced CD70 Expression in Patients with Rheumatoid Arthritis.International journal of molecular sciences · 2022Article
- The CD70-CD27 axis in oncology: the new kids on the block.Journal of experimental & clinical cancer research : CR · 2022Review
- CD70 as an actionable immunotherapeutic target in recurrent glioblastoma and its microenvironment.Journal for immunotherapy of cancer · 2022Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia-inducible factors (HIFs) facilitate cellular adaptation to environmental stress such as low oxygen conditions (hypoxia) and consequently promote tumor growth. While HIF-1α functions in cancer progression have been increasingly recognized, the contribution of HIF-2α remains widely unclear despite accumulating reports showing its overexpression in cancer cells. Here, we report that HIF-2α up-regulates the expression of CD70, a cancer-related surface antigen that improves anchorage-independent growth in cancer cells and is associated with poor clinical prognosis, which can be induced via epigenetic modifications mediated by DNMT1. The ablation of CD70 by RNAi led to decreased colony forming efficiency in soft agar. Most strikingly, we identified the emergence of CD70-expressing cells derived from CD70-negative cell lines upon prolonged hypoxia exposure or DNMT1 inhibition, both of which significantly reduced CpG-nucleotide methylations within CD70 promoter region. Interestingly, DNMT1 expression was decreased under hypoxia, which was rescued by HIF-2α knockdown. In addition, the expression of CD70 and colony forming efficiency in soft agar were decreased by knockdown of HIF-2α. These findings indicate that CD70 expression and an aggressive phenotype of cancer cells is driven under hypoxic conditions and mediated by HIF-2α functions and epigenetic modifications. This provides additional insights into the role of HIF-2α in coordinated regulation of stem-like functions and epigenetics that are important for cancer progression and may present additional targets for the development of novel combinatorial therapeutics.
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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.