ArticleThe Journal of biological chemistry2019
Inhibition of the deubiquitinase USP9x induces pre-B cell homeobox 1 (PBX1) degradation and thereby stimulates prostate cancer cell apoptosis.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 57 citations in OpenAlex.
- NTRK fusion in metastatic castration-resistant prostate cancer treated with entrectinib: a case report.Journal of medical case reports · 2026Article
- Targeting the PBX1-BCL2L1 axis as a therapeutic strategy in colorectal cancer.Cell death discovery · 2026Article
- Inhibition of the PI3K/AKT signaling pathway blocks the oncogenic activity of TRIM26 in prostate cancer cells.Asian journal of andrology · 2026Article
- Oncogenic Fusions HarboringCancers · 2025Review
- UBE2T promotes stage I lung adenocarcinoma progression through PBX1 ubiquitination and PBX1/RORA regulation.BMC cancer · 2024Article
- miR-377-3p Regulates Hippocampal Neurogenesis via the Zfp462-Pbx1 Pathway and Mediates Anxiety-Like Behaviors in Prenatal Hypoxic Offspring.Molecular neurobiology · 2024Article
- Molecular panorama of therapy resistance in prostate cancer: a pre-clinical and bioinformatics analysis for clinical translation.Cancer metastasis reviews · 2024Review
- PBX1: a TALE of two seasons-key roles during development and in cancer.Frontiers in cell and developmental biology · 2024Review
- Roles of USP9X in cellular functions and tumorigenesis (Review).Oncology letters · 2023Review
- Molecular Mechanisms of Lupus Susceptibility Allele PBX1D.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Article
- Protein degradation: expanding the toolbox to restrain cancer drug resistance.Journal of hematology & oncology · 2023Review
- TRIM26 promotes non-small cell lung cancer survival by inducing PBX1 degradation.International journal of biological sciences · 2023Article
- Review
- Unraveling the Potential Role of NEDD4-like E3 Ligases in Cancer.International journal of molecular sciences · 2022Review
- Molecular Landscape of LncRNAs in Prostate Cancer: A focus on pathways and therapeutic targets for intervention.Journal of experimental & clinical cancer research : CR · 2022Review
- Article
- Targeting autophagy in prostate cancer: preclinical and clinical evidence for therapeutic response.Journal of experimental & clinical cancer research : CR · 2022Review
- The regulation of PBXs and their emerging role in cancer.Journal of cellular and molecular medicine · 2022Review
- Pro-apoptotic and anti-apoptotic regulation mediated by deubiquitinating enzymes.Cellular and molecular life sciences : CMLS · 2022Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chemoresistance is a leading obstacle in effective management of advanced prostate cancer (PCa). A better understanding of the molecular mechanisms involved in PCa chemoresistance could improve treatment of patients with PCa. In the present study, using immune histochemical, chemistry, and precipitation assays with cells from individuals with benign or malignant prostate cancer or established PCa cell lines, we found that the oncogenic transcription factor pre-B cell leukemia homeobox-1 (PBX1) promotes PCa cell proliferation and confers to resistance against common anti-cancer drugs such as doxorubicin and cisplatin. We observed that genetic PBX1 knockdown abrogates this resistance, and further experiments revealed that PBX1 stability was modulated by the ubiquitin-proteasomal pathway. To directly probe the impact of this pathway on PBX1 activity, we screened for PBX1-specific deubiquitinases (Dubs) and found that ubiquitin-specific peptidase 9 X-linked (USP9x) interacted with and stabilized the PBX1 protein by attenuating its Lys-48-linked polyubiquitination. Moreover, the USP9x inhibitor WP1130 markedly induced PBX1 degradation and promoted PCa cell apoptosis. The results in this study indicate that PBX1 confers to PCa chemoresistance and identify USP9x as a Dub of PBX1. We concluded that targeting the USP9x/PBX1 axis could be a potential therapeutic strategy for managing advanced prostate cancer.
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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.