ArticleNature communications2019
IRE1α-XBP1s pathway promotes prostate cancer by activating c-MYC signaling.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 155 papers.
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Who cites it
155 citing papers in PubMed, 229 citations in OpenAlex.
- IRE1 activity is prognostic in localised and metastatic prostate cancer and affects epithelial lineage states.EMBO molecular medicine · 2026Article
- Regulatory Mechanisms of XBP1 in Tumorigenesis and Cancer Progression: Challenges and Therapeutic Strategies.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Synergistic Molecular Strategies for Targeting the Unfolded Protein Response in Cancer Therapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Targeting the IRE1α-XBP1 signaling axis impairs tumor growth and promotes myogenic differentiation in rhabdomyosarcoma.Communications biology · 2026Article
- Endoplasmic reticulum stress in antitumor immunity and immunotherapy resistance: mechanisms and therapeutic implications.Molecular cancer · 2026Review
- Targeting the IRE1α-XBP1 signaling axis impairs tumor growth and promotes myogenic differentiation in rhabdomyosarcoma.bioRxiv : the preprint server for biology · 2026Article
- Endoplasmic reticulum stress in disease pathogenesis: its implications for therapy.Signal transduction and targeted therapy · 2026Review
- ATF6 Identification Sensitizes B-Cell Precursor Acute Lymphoblastic Leukemia Cells to Doxorubicin.Current medical science · 2026Article
- Mechanistic insights and molecular therapy for neuroendocrine prostate cancer.Frontiers in oncology · 2026Review
- Prostate Cancer: Etiology, Diagnosis, and Treatment.Serican journal of medicine · 2026Article
- Targeting the unfolded protein response in cancer: mechanisms, small-molecule inhibitors, and translational challenges.Frontiers in immunology · 2026Review
- KIRA6 restrains the generation of myeloid-derived suppressor cells and overcomes resistance to anti-PD-1 therapy.Cell death & disease · 2025Article
- Targeting the unfolded protein response for cancer therapy: mitigating tumor adaptation and immune suppression.Biomarker research · 2025Review
- HSPA12B Protects Against Age-Related Endothelial Cell Senescence by Regulating STING Degradation.Aging cell · 2025Article
- The Unfolded Protein Response-Novel Mechanisms, Challenges, and Key Considerations for Therapeutic Intervention.Cancers · 2025Review
- TMEM166 negatively regulates unfolded protein response to affect hepatocellular carcinoma cell growth and sorafenib resistance.Cell death & disease · 2025Article
- Navigating the landscape of protein folding and proteostasis: from molecular chaperones to therapeutic innovations.Signal transduction and targeted therapy · 2025Review
- Protein disulfide isomerases regulate androgen receptor stability and promote prostate cancer cell growth and survival.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
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- Review
95 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
16 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of endoplasmic reticulum (ER) stress/the unfolded protein response (UPR) has been linked to cancer, but the molecular mechanisms are poorly understood and there is a paucity of reagents to translate this for cancer therapy. Here, we report that an IRE1α RNase-specific inhibitor, MKC8866, strongly inhibits prostate cancer (PCa) tumor growth as monotherapy in multiple preclinical models in mice and shows synergistic antitumor effects with current PCa drugs. Interestingly, global transcriptomic analysis reveal that IRE1α-XBP1s pathway activity is required for c-MYC signaling, one of the most highly activated oncogenic pathways in PCa. XBP1s is necessary for optimal c-MYC mRNA and protein expression, establishing, for the first time, a direct link between UPR and oncogene activation. In addition, an XBP1-specific gene expression signature is strongly associated with PCa prognosis. Our data establish IRE1α-XBP1s signaling as a central pathway in PCa and indicate that its targeting may offer novel treatment strategies.
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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.