ArticleClinical cancer research : an official journal of the American Association for Cancer Research2022
Acetylated HOXB13 Regulated Super Enhancer Genes Define Therapeutic Vulnerabilities of Castration-Resistant Prostate Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 22 citations in OpenAlex.
- Targeting the Androgen Receptor and Associated Cofactors in Prostate Cancer: Novel Approaches and Future Perspectives.International journal of molecular sciences · 2026Review
- A2AR as a key target for immune microenvironment remodeling in prostate cancer.Translational oncology · 2026Article
- Chromatin Accessibility in Cancer: Biological Functions, Mechanisms, Therapeutic Potential, and Future Directions.MedComm · 2026Review
- Genetic and epigenetic mechanisms underlying treatment-induced neuroendocrine prostate cancer.Journal of the National Cancer Center · 2026Review
- Prevalence and clinical significance of the rare HOXB13 X285K variant in a French Caribbean prostate cancer cohort.BMC cancer · 2025Article
- Comparative transcriptomics of salivary basal cell adenoma and adenocarcinoma sustain linear neoplastic evolution and intertumor heterogeneity: classification and biological implications.The Journal of pathology · 2025Article
- HOXB13 in cancer development: molecular mechanisms and clinical implications.Frontiers of medicine · 2025Review
- ACK1/TNK2 kinase: molecular mechanisms and emerging cancer therapeutics.Trends in pharmacological sciences · 2025Review
- SIRT3 Inhibits Cell Proliferation of Nonsmall Cell Lung Carcinoma by Inducing ROS Production.The clinical respiratory journal · 2024Article
- Prostate-Specific Membrane Antigen-Targeted Imaging and Its Correlation with HOXB13 Expression.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2024Article
- Clinical and Functional Analyses of an African-ancestry Gain-of-function HOXB13 Variant Implicated in Aggressive Prostate Cancer.European urology oncology · 2024Article
- Effects of super-enhancers in cancer metastasis: mechanisms and therapeutic targets.Molecular cancer · 2024Review
- Amino Terminal Acetylation of HOXB13 Regulates the DNA Damage Response in Prostate Cancer.Cancers · 2024Article
- Epigenetic underpinnings of tumor-immune dynamics in prostate cancer immune suppression.Trends in cancer · 2024Review
- The Impact of Circulating Tumor Cell HOXB13 RNA Detection in Men with Metastatic Castration-Resistant Prostate Cancer (mCRPC) Treated with Abiraterone or Enzalutamide.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Super-Enhancers and Their Parts: From Prediction Efforts to Pathognomonic Status.International journal of molecular sciences · 2024Review
- Genetic variant in a BaP-activated super-enhancer increases prostate cancer risk by promoting AhR-mediatedJournal of biomedical research · 2024Article
- Article
- Review
- Prostate cancer immunotherapy: Improving clinical outcomes with a multi-pronged approach.Cell reports. Medicine · 2023Review
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
purposeAndrogen receptor (AR) antagonism is exacerbated by HOXB13 in castration-resistant prostate cancers (CRPC). However, it is unclear when and how HOXB13 primes CRPCs for AR antagonism. By mass-spectrometry analysis of CRPC extract, we uncovered a novel lysine 13 (K13) acetylation in HOXB13 mediated by CBP/p300. To determine whether acetylated K13-HOXB13 is a clinical biomarker of CRPC development, we characterized its role in prostate cancer biology. EXPERIMENTAL
designWe identified tumor-specific acK13-HOXB13 signal enriched super enhancer (SE)-regulated targets. We analyzed the effect of loss of HOXB13K13-acetylation on chromatin binding, SE proximal target gene expression, self-renewal, enzalutamide sensitivity, and CRPC tumor growth by employing isogenic parental and HOXB13K13A mutants. Finally, using primary human prostate organoids, we evaluated whether inhibiting an acK13-HOXB13 target, ACK1, with a selective inhibitor (R)-9b is superior to AR antagonists in inhibiting CRPC growth.
resultsacK13-HOXB13 promotes increased expression of lineage (AR, HOXB13), prostate cancer diagnostic (FOLH1), CRPC-promoting (ACK1), and angiogenesis (VEGFA, Angiopoietins) genes early in prostate cancer development by establishing tumor-specific SEs. acK13-HOXB13 recruitment to key SE-regulated targets is insensitive to enzalutamide. ACK1 expression is significantly reduced in the loss of function HOXB13K13A mutant CRPCs. Consequently, HOXB13K13A mutants display reduced self-renewal, increased sensitivity to enzalutamide, and impaired xenograft tumor growth. Primary human prostate tumor organoids expressing HOXB13 are significantly resistant to AR antagonists but sensitive to (R)-9b.
conclusionsIn summary, acetylated HOXB13 is a biomarker of clinically significant prostate cancer. Importantly, PSMA-targeting agents and (R)-9b could be new therapeutic modalities to target HOXB13-ACK1 axis regulated prostate cancers.
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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.