ArticleCell death and differentiation2024
Hypoxia-activated XBP1s recruits HDAC2-EZH2 to engage epigenetic suppression of ΔNp63α expression and promote breast cancer metastasis independent of HIF1α.
Article in Cell death and differentiation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Multimodal deep learning for predicting neoadjuvant treatment outcomes in breast cancer: a systematic review.Biology direct · 2025Pooled it
- A label-free supramolecular nanoassembly triggers multi-organelle crosstalk-dependent metastasis inhibition via nuclear ROS-HDAC2 axis.Materials today. Bio · 2026Article
- The histone deacetylase family in health and disease.Signal transduction and targeted therapy · 2026Review
- QRICH1 Suppresses Glioma Progression by Inducing ER Stress and Activating the PERK-ATF4-CHOP Pathway.Cancer medicine · 2026Article
- Translational issues with phototherapy of cancer.Translational oncology · 2026Review
- Targeting enolase isoenzyme 2 enables precision glycolysis inhibition in VHL-mutant renal cell carcinoma.Cell death & disease · 2026Article
- The impactful role of the HDACs in the regulation of gene expression and as targets for disease therapy.Science advances · 2026Review
- Hypoxia-induced endoplasmic reticulum stress mediates lenvatinib resistance in hepatocellular carcinoma through the IRE1α-XBP1s-HIF1α pathway.Journal of cancer research and clinical oncology · 2026Article
- Hypoxia-induced XBP1s-MYDGF axis suppresses ferroptosis through UBQLN1-mediated stabilization of LCN2 in gastric cancer.Oncogene · 2026Article
- Activation of unfolded protein response pathways promotes keratinocyte differentiation and ameliorates psoriasis phenotypes.Cell stress & chaperones · 2026Article
- TRIM29 suppresses malignant progression in lung squamous cell carcinoma by shaping an immunosuppressive tumor microenvironment.Scientific reports · 2026Article
- ΔNp63α drives serine synthesis to promote carboplatin resistance in NSCLC.Cell death & disease · 2026Article
- Overcoming immunotherapy resistance in breast cancer: a novel strategy by targeting the integrated stress response.Frontiers in cell and developmental biology · 2026Review
- HDAC2 as a therapeutic target in bladder cancer: insights into the altered epigenetic regulation and lysine lactylation.Journal of experimental & clinical cancer research : CR · 2025Article
- SOX2 transactivates NRF2 to promote carboplatin resistance in lung squamous cell carcinoma.Acta biochimica et biophysica Sinica · 2025Article
- From 2D to 3D: transforming malignant bone tumor research with advanced culture models.Journal of Zhejiang University. Science. B · 2025Review
- EZH2 suppresses the chemosensitivity of diffuse large B cell lymphoma via regulating TP53INP1.Clinical and experimental medicine · 2025Article
- Epigenetic regulation by DNA methylation, histone modifications and chromatin remodeling complexes in controlling spermatogenesis and their dysfunction with male infertility.Cellular and molecular life sciences : CMLS · 2025Review
- Precision epigenetic therapies in oncology.Cancer metastasis reviews · 2025Review
- Impaired autophagy by cepharanthine induces immunogenic cell death and enhances anti-PD-1 response in MSS-type colorectal cancer.Oncogene · 2025Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Hypoxia is a hallmark of cancer development. However, the molecular mechanisms by which hypoxia promotes tumor metastasis are not fully understood. In this study, we demonstrate that hypoxia promotes breast cancer metastasis through suppression of ΔNp63α in a HIF1α-independent manner. We show that hypoxia-activated XBP1s forms a stable repressor protein complex with HDAC2 and EZH2 to suppress ΔNp63α transcription. Notably, H3K27ac is predominantly occupied on the ΔNp63 promoter under normoxia, while H3K27me3 on the promoter under hypoxia. We show that XBP1s binds to the ΔNp63 promoter to recruit HDAC2 and EZH2 in facilitating the switch of H3K27ac to H3K27me3. Pharmacological inhibition or the knockdown of either HDAC2 or EZH2 leads to increased H3K27ac, accompanied by the reduced H3K27me3 and restoration of ΔNp63α expression suppressed by hypoxia, resulting in inhibition of cell migration. Furthermore, the pharmacological inhibition of IRE1α, but not HIF1α, upregulates ΔNp63α expression in vitro and inhibits tumor metastasis in vivo. Clinical analyses reveal that reduced p63 expression is correlated with the elevated expression of XBP1, HDAC2, or EZH2, and is associated with poor overall survival in human breast cancer patients. Together, these results indicate that hypoxia-activated XBP1s modulates the epigenetic program in suppression of ΔNp63α to promote breast cancer metastasis independent of HIF1α and provides a molecular basis for targeting the XBP1s/HDAC2/EZH2-ΔNp63α axis as a putative strategy in the treatment of breast cancer metastasis.
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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.