ArticleCancer cell2015
DNA-PKcs-Mediated Transcriptional Regulation Drives Prostate Cancer Progression and Metastasis.
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Article in Cancer cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers.
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120citing papers in PubMed
9.8field-weighted citation impact, top 1% of its field
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Who cites it
120 citing papers in PubMed, 177 citations in OpenAlex.
- Phase Ib/II Study of Enzalutamide with Samotolisib (LY3023414) or Placebo in Patients with Metastatic Castration-Resistant Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- Biomarker analysis of the MITO2 phase III trial of first-line treatment in ovarian cancer: predictive value of DNA-PK and phosphorylated ACC.Oncotarget · 2016Trial
- CDK12/13 Inhibition Induces DNA Hypomethylation and Sensitizes Cancer Cells to Compounds Targeting DNA-PK.Journal of cellular and molecular medicine · 2026Article
- Targeting DNA-PK: medicinal chemistry insights into small-molecule inhibitor discovery and optimisation.RSC medicinal chemistry · 2026Review
- DNA-PKcs inhibition sensitizes glioblastoma to radiotherapy through reprogramming of tumor cell states and immune microenvironment cell types.Research square · 2026Article
- PARP inhibition and pharmacological ascorbate demonstrate synergy in castration-resistant prostate cancer.Molecular oncology · 2026Article
- A Pan-Cancer Multi-Omics Analysis of CAD: Integrating CRISPR and Metabolomics Data to Unravel the Metabolic-Immune Axis and Immunotherapy Response.Biomedicines · 2026Article
- Synergistic Effects of DNA-PKcs Inhibition and Radiotherapy in Esophageal Squamous Cell Carcinoma.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Acquired resistance of cancer therapies: Mechanisms and perspectives.Chinese medical journal · 2026Review
- Transcriptomic analysis to uncover the mechanism of radiosensitization of AR-positive triple-negative breast cancers with AR inhibition.NPJ breast cancer · 2026Article
- Identification of CAND1 as a DNA-dependent protein kinase-regulated coactivator of androgen receptor and the ARv7 splice variant.PloS one · 2026Article
- Vemurafenib, cetuximab and camrelizumab in BRAF V600E-mutated/MSS metastatic colorectal cancer.Journal of translational medicine · 2025Article
- The interconnection between androgen receptor and DNA damage response pathways in prostate cancer.Current urology · 2025Review
- DNA-PKcs, a player winding and dancing with RNA metabolism and diseases.Cellular & molecular biology letters · 2025Review
- In vivo investigation of STN1 downregulation in melanoma formation in adult mice following UV irradiation.PloS one · 2025Article
- Disruption of RNA Splicing Increases Vulnerability of Cells to DNA-PK Inhibitors.International journal of molecular sciences · 2024Article
- Article
- The DNA repair protein DNA-PKcs modulates synaptic plasticity via PSD-95 phosphorylation and stability.EMBO reports · 2024Article
- Secrets of DNA-PKcs beyond DNA repair.NPJ precision oncology · 2024Review
- The multifaceted functions of DNA-PKcs: implications for the therapy of human diseases.MedComm · 2024Review
60 more citing papers are in PubMed but not listed here.
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Authors and funding
29 authors at 9 institutions in 1 country.
Jonathan F GoodwinDepartment of Cancer Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Vishal KothariDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, USA.
Justin M DrakeDepartments of Microbiology, Immunology, & Molecular Genetics, UCLA, Los Angeles, CA 90095, USA.
Shuang ZhaoDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, USA.
Emanuela DylgjeriDepartment of Cancer Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Jeffry L DeanDepartment of Cancer Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Matthew J SchiewerDepartment of Cancer Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Christopher McNairDepartment of Cancer Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Jennifer K JonesDepartment of Cancer Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Alvaro AytesDepartments of Urology, Pathology & Cell Biology, Systems Biology, Institute for Cancer Genetics, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA.
Michael S MageeDepartment of Pharmacology & Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Adam E SnookDepartment of Pharmacology & Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Ziqi ZhuDepartment of Cancer Biology, Cleveland Clinic, Cleveland, OH 44195, USA.
Robert B DenDepartment of Cancer Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA; Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA 19107, USA; Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Ruth C BirbeDepartment of Pathology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Leonard G GomellaDepartment of Urology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Nicholas A GrahamCrump Institute for Molecular Imaging, UCLA, Los Angeles, CA 90095, USA; Department of Molecular & Medical Pharmacology, UCLA, Los Angeles, CA 90095, USA.
Ajay A VashishtDepartment of Biological Chemistry, UCLA, Los Angeles, CA 90095, USA.
James A WohlschlegelDepartment of Biological Chemistry, UCLA, Los Angeles, CA 90095, USA.
Thomas G GraeberCrump Institute for Molecular Imaging, UCLA, Los Angeles, CA 90095, USA; Department of Molecular & Medical Pharmacology, UCLA, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA 90095, USA; California NanoSystems Institute, UCLA, Los Angeles, CA 90095, USA.
R Jeffrey KarnesDepartment of Urology, Mayo Clinic, Rochester, MN 55902, USA.
Mandeep TakharGenomeDx Biosciences, San Diego, CA 92121, USA.
Elai DavicioniGenomeDx Biosciences, San Diego, CA 92121, USA.
Scott A TomlinsMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Urology, University of Michigan, Ann Arbor, MI 48109, USA; Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA.
Cory Abate-ShenDepartments of Urology, Pathology & Cell Biology, Systems Biology, Institute for Cancer Genetics, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA.
Nima SharifiDepartment of Cancer Biology, Cleveland Clinic, Cleveland, OH 44195, USA; Department of Urology, Cleveland Clinic, Cleveland, OH 44195, USA; Solid Tumor Oncology, Cleveland Clinic, Cleveland, OH 44195, USA.
Owen N WitteDepartments of Microbiology, Immunology, & Molecular Genetics, UCLA, Los Angeles, CA 90095, USA; Department of Molecular & Medical Pharmacology, UCLA, Los Angeles, CA 90095, USA; Howard Hughes Medical Institute, UCLA, Los Angeles, CA 90095, USA; Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, CA 90095, USA.
Felix Y FengMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, USA; Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA.
Karen E KnudsenDepartment of Cancer Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA; Department of Urology, Thomas Jefferson University, Philadelphia, PA 19107, USA; Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA 19107, USA; Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA. Electronic address: karen.knudsen@jefferson.edu.
Thomas Jefferson University · USUniversity of Michigan · USUniversity of California, Los Angeles · USCleveland Clinic · USColumbia University Irving Medical Center · USCalifornia NanoSystems Institute · USHoward Hughes Medical Institute · USMayo Clinic in Arizona · USUCLA Medical Center · US
Funding
X-Ray Crystallography and Macromolecular CharacterizationP30CA056036 · NCI · THOMAS JEFFERSON UNIVERSITY · PI DANIEL P SILVER · 1995 to 2026
$94.8MUCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0MTARGETED COMBINATORIAL TREATMENT OF BRAF MELANOMASP01CA168585 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI RIBAS, ANTONI · 2013 to 2017
$8.4MPreclinical analyses of advanced prostate cancer in genetically-engineered miceR01CA173481 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Cory Abate-Shen · 2013 to 2026
$6.1MUCLA Scholars in Oncologic Molecular lmaging (SOMI)R25CA098010 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PHELPS, MICHAEL E · 2003 to 2013
$5.0MMolecular mechanisms of prostate cancer metastasisR01CA183929 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ABATE-SHEN, CORY · 2015 to 2025
$4.1MProteolytic Control of Iron Metabolism by the Ubiquitin Ligase FBXL5R01GM089778 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WOHLSCHLEGEL, JAMES AKIRA · 2010 to 2023
$4.0MRB Function in Prostate Cancer ProgressionR01CA176401 · NCI · THOMAS JEFFERSON UNIVERSITY · PI KNUDSEN, KAREN E · 2014 to 2018
$2.2MSWI/SNF dysregulation in development and diseaseR01CA159945 · NCI · THOMAS JEFFERSON UNIVERSITY · PI KNUDSEN, KAREN E · 2012 to 2016
$1.6MNCATS NIH HHS UL1 TR000124NCATS NIH HHS UL1TR000124NCI NIH HHS CA159945NCI NIH HHS CA168585NCI NIH HHS CA173481NCI NIH HHS CA176401NCI NIH HHS CA183929NCI NIH HHS P01 CA168585NCI NIH HHS P30 CA056036NCI NIH HHS R01 CA159945NCI NIH HHS R01 CA173481NCI NIH HHS R01 CA176401NCI NIH HHS R01 CA183929NCI NIH HHS R25 CA098010NCI NIH HHS R25T CA098010NIGMS NIH HHS GM089778NIGMS NIH HHS R01 GM089778
Abstract
Emerging evidence demonstrates that the DNA repair kinase DNA-PKcs exerts divergent roles in transcriptional regulation of unsolved consequence. Here, in vitro and in vivo interrogation demonstrate that DNA-PKcs functions as a selective modulator of transcriptional networks that induce cell migration, invasion, and metastasis. Accordingly, suppression of DNA-PKcs inhibits tumor metastases. Clinical assessment revealed that DNA-PKcs is significantly elevated in advanced disease and independently predicts for metastases, recurrence, and reduced overall survival. Further investigation demonstrated that DNA-PKcs in advanced tumors is highly activated, independent of DNA damage indicators. Combined, these findings reveal unexpected DNA-PKcs functions, identify DNA-PKcs as a potent driver of tumor progression and metastases, and nominate DNA-PKcs as a therapeutic target for advanced malignancies.
Indexed as
AnimalsCell Line, TumorDNA-Activated Protein KinaseDNA-Binding ProteinsGene Expression Regulation, NeoplasticGene Regulatory NetworksHumansMaleMiceMolecular Sequence DataNeoplasm InvasivenessNeoplasm TransplantationNuclear ProteinsProstatic NeoplasmsReceptors, AndrogenAR protein, humanDNA-Activated Protein KinaseDNA-Binding ProteinsNuclear ProteinsPrkdc protein, mouseReceptors, Androgen
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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.