ArticleCancer discovery2021
NKX3.1 Localization to Mitochondria Suppresses Prostate Cancer Initiation.
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Article in Cancer discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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31citing papers in PubMed, 1 pooled it
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31 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Association Aamong Ppolymorphisms in the Aapoptosis-Rrelated NKX3-1, Caspase-3, Caspase-9, and BCL-2 Genes and Prostate Cancer Susceptibility From 9706 Cases and 12,567 Controls.Cancer reports (Hoboken, N.J.) · 2025Pooled it
- A forward genetic screen identifies Sirtuin1 as a driver of neuroendocrine prostate cancer.The Journal of experimental medicine · 2026Article
- Exogenous testosterone exacerbates pre-neoplastic lesions in the prostate of NKX3.1-deficient mice.Laboratory animal research · 2026Article
- Prostatic fibroblast reprogramming by Interleukin-30 activates prostate cancer metastasis programs.Molecular biomedicine · 2026Article
- Dysregulation of the urea cycle - potential targets for treatment and diagnosis in prostate cancer.Expert reviews in molecular medicine · 2026Review
- Deciphering the Genomic Landscape of Renal Cell Carcinoma Brain Metastases.bioRxiv : the preprint server for biology · 2026Article
- Single- and Multi-Trait GWASs Combined with Genetic Parameter Estimation Reveal Candidate Genes for Body Conformation Traits in Sika Deer (Animals : an open access journal from MDPI · 2026Article
- Mitochondria-transliterated ALDH1L1 functions as a feedback regulator of redox homeostasis in cancer cells to enhance the resistance to pro-oxidative therapy.Cell death and differentiation · 2026Article
- Identification and validation of critical mitochondrial hub genes for prostate cancer.Oncology letters · 2026Article
- Identifying drug targets and evaluating KLK3-targeted inhibitors for prostate cancer using in-silico and in-vitro approaches.Medical oncology (Northwood, London, England) · 2025Article
- The Homeobox Transcription Factor NKX3.1 Displays an Oncogenic Role in Castration-Resistant Prostate Cancer Cells.Cancers · 2025Article
- Mitochondrial fission process 1 protein: a comprehensive review of its core roles in mitochondrial dynamics, disease, and therapeutic targets.Frontiers in cell and developmental biology · 2025Review
- Single nucleotide polymorphisms ofAnimal biotechnology · 2024Article
- Mitochondrial GCN5L1 acts as a novel regulator for iron homeostasis to promote sorafenib sensitivity in hepatocellular carcinoma.Journal of translational medicine · 2024Article
- About metformin and its action on the mitochondrial respiratory chain in prostate cancer.Translational andrology and urology · 2024Article
- Mechanism-centric regulatory network identifies NME2 and MYC programs as markers of Enzalutamide resistance in CRPC.Nature communications · 2024Article
- SUMO E3 ligase MUL1 inhibits lymph node metastasis of bladder cancer by mediating mitochondrial HSPA9 translocation.International journal of biological sciences · 2024Article
- Association of HLA-A*11:01, -A*24:02, and -B*18:01 with Prostate Cancer Risk: A Case-Control Study.International journal of molecular sciences · 2023Article
- Mitochondrial carrier 1 (MTCH1) governs ferroptosis by triggering the FoxO1-GPX4 axis-mediated retrograde signaling in cervical cancer cells.Cell death & disease · 2023Article
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Authors and funding
23 authors at 4 institutions in 3 countries.
Alexandros Papachristodoulou *Department of Molecular Pharmacology and Therapeutics, Columbia University Irving Medical Center, New York, New York.ORCID 0000-0001-8488-7785
Antonio Rodriguez-CaleroDepartment of Biomedical Research, University of Bern, Bern, Switzerland.ORCID 0000-0002-2744-2381
Sukanya PanjaDepartment of Health Informatics, Rutgers School of Health Professions, Rutgers Biomedical and Health Sciences, Newark, New Jersey.
Elizabeth MargolskeeDepartment of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York.
Renu K VirkDepartment of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York.
Teresa A MilnerFeil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York.ORCID 0000-0002-0458-6569
Luis Pina MartinaDepartment of Molecular Pharmacology and Therapeutics, Columbia University Irving Medical Center, New York, New York.
Jaime Y KimDepartment of Molecular Pharmacology and Therapeutics, Columbia University Irving Medical Center, New York, New York.
Matteo Di BernardoDepartment of Molecular Pharmacology and Therapeutics, Columbia University Irving Medical Center, New York, New York.ORCID 0000-0002-7574-1941
Alanna B WilliamsDepartment of Medicine, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, New York.
Elvis A MalizaDepartment of Molecular Pharmacology and Therapeutics, Columbia University Irving Medical Center, New York, New York.
Joseph M CaputoDepartment of Urology, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, New York.ORCID 0000-0001-6793-8288
Christopher HaasDepartment of Urology, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, New York.
Vinson WangDepartment of Urology, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, New York.
Guarionex Joel De CastroDepartment of Urology, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, New York.
Sven WenskeDepartment of Urology, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, New York.
Hanina HibshooshDepartment of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York.
James M McKiernanDepartment of Urology, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, New York.
Michael M ShenDepartment of Urology, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, New York.ORCID 0000-0002-4042-1657
Mark A RubinDepartment of Biomedical Research, University of Bern, Bern, Switzerland.ORCID 0000-0002-8321-9950
Antonina MitrofanovaDepartment of Health Informatics, Rutgers School of Health Professions, Rutgers Biomedical and Health Sciences, Newark, New Jersey.
Aditya Dutta *Department of Molecular Pharmacology and Therapeutics, Columbia University Irving Medical Center, New York, New York. cabateshen@columbia.edu adidutta@udel.edu.ORCID 0000-0001-9007-4262
Cory Abate-ShenDepartment of Molecular Pharmacology and Therapeutics, Columbia University Irving Medical Center, New York, New York. cabateshen@columbia.edu adidutta@udel.edu.
Columbia University Irving Medical Center · USRutgers, The State University of New Jersey · USUniversity of Bern · CHCornell University · US
Funding
Tumor Biology and Microenvironment ProgramP30CA013696 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI Anil K Rustgi · 1985 to 2026
$115.3MClinical and Translational Science AwardUL1TR000040 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2012 to 2015
$26.2MULTRASTRUCTURAL INTERACTIONS OF OPIOIDS IN HIPPOCAMPUSR01DA008259 · NIDA · WEILL MEDICAL COLL OF CORNELL UNIV · PI MILNER, TERESA A · 1993 to 2019
$6.4MPreclinical analyses of advanced prostate cancer in genetically-engineered miceR01CA173481 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Cory Abate-Shen · 2013 to 2026
$6.1MMolecular mechanisms of prostate cancer metastasisR01CA183929 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ABATE-SHEN, CORY · 2015 to 2025
$4.1MInvestigating the cell of origin for bladder cancerR01CA193442 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ABATE-SHEN, CORY · 2015 to 2019
$2.4MAnalysis of epithelial heterogeneity in prostate development and cancerR01CA238005 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI SHEN, MICHAEL M. · 2019 to 2023
$2.1MMitochondrial and nuclear functions of NKX3.1 in regulating oxidative stress in prostate cancerR01CA233176 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ABATE-SHEN, CORY · 2019 to 2023
$1.9MAnalysis of drug response in organoids and mouse modelsR01CA196662 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ABATE-SHEN, CORY, SHEN, MICHAEL M. · 2016 to 2018
$1.8MMENOPAUSAL CHANGES IN HYPOTHALAMUS AND HYPERTENSION SUSCEPTIBILITYR01HL098351 · NHLBI · WEILL MEDICAL COLL OF CORNELL UNIV · PI MILNER, TERESA A · 2011 to 2014
$1.7MGeneralizable biomedical informatics strategies for predictive modeling of treatment responseR01LM013236 · NLM · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · PI MITROFANOVA, ANTONINA · 2020 to 2023
$1.3MNCATS NIH HHS UL1 TR000040NCI NIH HHS P30 CA013696NCI NIH HHS R01 CA173481NCI NIH HHS R01 CA183929NCI NIH HHS R01 CA193442NCI NIH HHS R01 CA196662NCI NIH HHS R01 CA233176NCI NIH HHS R01 CA238005NHLBI NIH HHS R01 HL098351NIDA NIH HHS R01 DA008259NLM NIH HHS R01 LM013236Swiss National Science Foundation 181557
Abstract
Mitochondria provide the first line of defense against the tumor-promoting effects of oxidative stress. Here we show that the prostate-specific homeoprotein NKX3.1 suppresses prostate cancer initiation by protecting mitochondria from oxidative stress. Integrating analyses of genetically engineered mouse models, human prostate cancer cells, and human prostate cancer organotypic cultures, we find that, in response to oxidative stress, NKX3.1 is imported to mitochondria via the chaperone protein HSPA9, where it regulates transcription of mitochondrial-encoded electron transport chain (ETC) genes, thereby restoring oxidative phosphorylation and preventing cancer initiation. Germline polymorphisms of
Indexed as
Gene Expression Regulation, NeoplasticCell Line, TumorHomeodomain ProteinsHumansMaleMitochondriaProstatic NeoplasmsTranscription FactorsHomeodomain ProteinsNKX3-1 protein, humanTranscription Factors
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