ArticleEMBO molecular medicine2015
Divergent androgen regulation of unfolded protein response pathways drives prostate cancer.
Article in EMBO molecular medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 108 citations in OpenAlex.
- IRE1 activity is prognostic in localised and metastatic prostate cancer and affects epithelial lineage states.EMBO molecular medicine · 2026Article
- Mechanistic insights and molecular therapy for neuroendocrine prostate cancer.Frontiers in oncology · 2026Review
- Targeting the unfolded protein response for cancer therapy: mitigating tumor adaptation and immune suppression.Biomarker research · 2025Review
- Navigating the landscape of protein folding and proteostasis: from molecular chaperones to therapeutic innovations.Signal transduction and targeted therapy · 2025Review
- Article
- Harnessing indole scaffolds to identify small-molecule IRE1α inhibitors modulating XBP1 mRNA splicing.Nature communications · 2025Article
- Oxidative stress as a catalyst in prostate cancer progression: unraveling molecular mechanisms and exploring therapeutic interventions.Discover oncology · 2025Review
- DPH2 is a biomarker associated with cell death, immunity and prognosis based on pan-cancer analysis.Discover oncology · 2025Article
- Modulating Endoplasmic Reticulum Stress in Gastrointestinal Cancers: Insights from Traditional Chinese Medicine.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Targeting IRE1α reprograms the tumor microenvironment and enhances anti-tumor immunity in prostate cancer.Nature communications · 2024Article
- Mitochondrial Elongation and ROS-Mediated Apoptosis in Prostate Cancer Cells under Therapy with Apalutamide and Complex I Inhibitor.International journal of molecular sciences · 2024Article
- Adaptations of membrane trafficking in cancer and tumorigenesis.Journal of cell science · 2024Review
- Targeting the IRE1α-XBP1s axis confers selective vulnerability in hepatocellular carcinoma with activated Wnt signaling.Oncogene · 2024Article
- Metabolic reprogramming directed by super-enhancers in tumors: An emerging landscape.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
- Proteome-Wide Profiling Using Sample Multiplexing of a Human Cell Line Treated with Cannabidiol (CBD) and Tetrahydrocannabinol (THC).Proteomes · 2023Article
- Estrogens drive the endoplasmic reticulum-associated degradation and promote proto-oncogene c-Myc expression in prostate cancer cells by androgen receptor/estrogen receptor signaling.Journal of cell communication and signaling · 2023Article
- Prolyl 4-hydroxylase subunit beta (P4HB) could serve as a prognostic and radiosensitivity biomarker for prostate cancer patients.European journal of medical research · 2023Article
- Article
- Loss of ATF6α in a human carcinoma cell line is compensated not by its paralogue ATF6β but by sustained activation of the IRE1 and PERK arms for tumor growth in nude mice.Molecular biology of the cell · 2023Article
- A compendium of Androgen Receptor Variant 7 target genes and their role in Castration Resistant Prostate Cancer.Frontiers in oncology · 2023Review
1 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The unfolded protein response (UPR) is a homeostatic mechanism to maintain endoplasmic reticulum (ER) function. The UPR is activated by various physiological conditions as well as in disease states, such as cancer. As androgens regulate secretion and development of the normal prostate and drive prostate cancer (PCa) growth, they may affect UPR pathways. Here, we show that the canonical UPR pathways are directly and divergently regulated by androgens in PCa cells, through the androgen receptor (AR), which is critical for PCa survival. AR bound to gene regulatory sites and activated the IRE1α branch, but simultaneously inhibited PERK signaling. Inhibition of the IRE1α arm profoundly reduced PCa cell growth in vitro as well as tumor formation in preclinical models of PCa in vivo. Consistently, AR and UPR gene expression were correlated in human PCa, and spliced XBP-1 expression was significantly upregulated in cancer compared with normal prostate. These data establish a genetic switch orchestrated by AR that divergently regulates the UPR pathways and suggest that targeting IRE1α signaling may have therapeutic utility in PCa.
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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.