ArticleThe Journal of biological chemistry2012
Ack1-mediated androgen receptor phosphorylation modulates radiation resistance in castration-resistant prostate cancer.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 97 citations in OpenAlex.
- ACK1 condensates promote STAT5 signaling in lung squamous cell carcinoma.Cancer cell international · 2025Article
- The activated tyrosine kinase ACK1 by multiple receptor tyrosine kinases promotes proliferation and invasion of mesothelioma via regulation of PI3K/AKT/mTOR and RAF/MAPK signaling pathways.Cancer gene therapy · 2025Article
- ACK1/TNK2 kinase: molecular mechanisms and emerging cancer therapeutics.Trends in pharmacological sciences · 2025Review
- Article
- SHP2 as a primordial epigenetic enzyme expunges histone H3 pTyr-54 to amend androgen receptor homeostasis.Nature communications · 2024Article
- ACK1 and BRK non-receptor tyrosine kinase deficiencies are associated with familial systemic lupus and involved in efferocytosis.medRxiv : the preprint server for health sciences · 2024Article
- Epigenetic underpinnings of tumor-immune dynamics in prostate cancer immune suppression.Trends in cancer · 2024Review
- Integrating Clinical Cancer and PTM Proteomics Data Identifies a Mechanism of ACK1 Kinase Activation.Molecular cancer research : MCR · 2024Article
- HSP27 Modulates Neuropathic Pain by Inhibiting P2X3 Degradation.Molecular neurobiology · 2024Article
- ACKnowledging the role of the Activated-Cdc42 associated kinase (ACK) in regulating protein stability in cancer.Small GTPases · 2023Review
- Prostate cancer immunotherapy: Improving clinical outcomes with a multi-pronged approach.Cell reports. Medicine · 2023Review
- Epigenetic reprogramming of cell cycle genes by ACK1 promotes breast cancer resistance to CDK4/6 inhibitor.Oncogene · 2023Article
- Histone H2A Lys130 acetylation epigenetically regulates androgen production in prostate cancer.Nature communications · 2023Article
- Review
- mCRPC Patients ReceivingJournal of nuclear medicine : official publication, Society of Nuclear Medicine · 2022Article
- Acetylated HOXB13 Regulated Super Enhancer Genes Define Therapeutic Vulnerabilities of Castration-Resistant Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Chronologically modified androgen receptor in recurrent castration-resistant prostate cancer and its therapeutic targeting.Science translational medicine · 2022Article
- Assembly of nuclear dimers of PI3K regulatory subunits is regulated by the Cdc42-activated tyrosine kinase ACK.The Journal of biological chemistry · 2022Article
- Review
- Choosing Kinase Inhibitors for Androgen Deprivation Therapy-Resistant Prostate Cancer.Pharmaceutics · 2022Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Androgen deprivation therapy has been the standard of care in prostate cancer due to its effectiveness in initial stages. However, the disease recurs, and this recurrent cancer is referred to as castration-resistant prostate cancer (CRPC). Radiotherapy is the treatment of choice; however, in addition to androgen independence, CRPC is often resistant to radiotherapy, making radioresistant CRPC an incurable disease. The molecular mechanisms by which CRPC cells acquire radioresistance are unclear. Androgen receptor (AR)-tyrosine 267 phosphorylation by Ack1 tyrosine kinase (also known as TNK2) has emerged as an important mechanism of CRPC growth. Here, we demonstrate that pTyr(267)-AR is recruited to the ATM (ataxia telangiectasia mutated) enhancer in an Ack1-dependent manner to up-regulate ATM expression. Mice engineered to express activated Ack1 exhibited a significant increase in pTyr(267)-AR and ATM levels. Furthermore, primary human CRPCs with up-regulated activated Ack1 and pTyr(267)-AR also exhibited significant increase in ATM expression. The Ack1 inhibitor AIM-100 not only inhibited Ack1 activity but also was able to suppress AR Tyr(267) phosphorylation and its recruitment to the ATM enhancer. Notably, AIM-100 suppressed Ack1 mediated ATM expression and mitigated the growth of radioresistant CRPC tumors. Thus, our study uncovers a previously unknown mechanism of radioresistance in CRPC, which can be therapeutically reversed by a new synergistic approach that includes radiotherapy along with the suppression of Ack1/AR/ATM signaling by the Ack1 inhibitor, AIM-100.
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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.