ArticleEMBO reports2023
ZBTB2 links p53 deficiency to HIF-1-mediated hypoxia signaling to promote cancer aggressiveness.
Article in EMBO reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 11 citations in OpenAlex.
- The lariat RNA debranching enzyme DBR1 enhances HIF-1 signaling and chemoresistance at the expense of lariat RNA processing.The Journal of biological chemistry · 2026Article
- Development of a model to predict high-risk histopathological features in early T-stage lung adenocarcinoma using thin-slice CT and FDG-PET/CT parameters for selecting optimal candidates for sub-lobar resection.Journal of thoracic disease · 2026Article
- Metabolic reprogramming in cancer: dysregulation of glucose, lipid, and amino acid pathways and therapeutic opportunities.Molecular biomedicine · 2026Review
- circ-UBR5 in hypoxia-induced exosomes may mediate lung adenocarcinoma metastasis via the targeting of HNRNPR.Translational lung cancer research · 2026Article
- Preliminary Exploration of Fluvastatin Inhibiting Proliferation, Migration and Invasion of Lung Cancer Cells and Reversing Paclitaxel Resistance: Mechanism Exploration Based on Multi-Omics Analysis.Drug design, development and therapy · 2026Article
- Integrating Hypoxia Signatures from scRNA-seq and Bulk Transcriptomes for Prognosis Prediction and Precision Therapy in Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma.International journal of molecular sciences · 2025Article
- Article
- ZBTB2 links p53 deficiency to HIF-1-mediated hypoxia signaling to promote cancer aggressiveness.EMBO reports · 2023Article
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Authors and funding
18 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aberrant activation of the hypoxia-inducible transcription factor HIF-1 and dysfunction of the tumor suppressor p53 have been reported to induce malignant phenotypes and therapy resistance of cancers. However, their mechanistic and functional relationship remains largely unknown. Here, we reveal a mechanism by which p53 deficiency triggers the activation of HIF-1-dependent hypoxia signaling and identify zinc finger and BTB domain-containing protein 2 (ZBTB2) as an important mediator. ZBTB2 forms homodimers via its N-terminus region and increases the transactivation activity of HIF-1 only when functional p53 is absent. The ZBTB2 homodimer facilitates invasion, distant metastasis, and growth of p53-deficient, but not p53-proficient, cancers. The intratumoral expression levels of ZBTB2 are associated with poor prognosis in lung cancer patients. ZBTB2 N-terminus-mimetic polypeptides competitively inhibit ZBTB2 homodimerization and significantly suppress the ZBTB2-HIF-1 axis, leading to antitumor effects. Our data reveal an important link between aberrant activation of hypoxia signaling and loss of a tumor suppressor and provide a rationale for targeting a key mediator, ZBTB2, to suppress cancer aggressiveness.
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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.