ArticleNature medicine2015
Active Pin1 is a key target of all-trans retinoic acid in acute promyelocytic leukemia and breast cancer.
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Article in Nature medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 160 papers.
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160citing papers in PubMed
12.5field-weighted citation impact, top 1% of its field
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Who cites it
160 citing papers in PubMed, 267 citations in OpenAlex.
- Combined FOLFOX4 with all-trans retinoic acid versus FOLFOX4 with placebo in treatment of advanced hepatocellular carcinoma with extrahepatic metastasis: a randomized, double-blind comparative study.Signal transduction and targeted therapy · 2023Trial
- The IL-33-PIN1-IRAK-M axis is critical for type 2 immunity in IL-33-induced allergic airway inflammation.Nature communications · 2018Trial
- Targeting MYC-Driven Cancers: From Oncogenic Addiction to Therapeutic Vulnerability.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- The Effect of Prolyl Isomerase Pin1 on the Development of Metabolic Dysfunction-Associated Steatohepatitis and a New Treatment Strategy.International journal of molecular sciences · 2026Review
- Vitamin A and its analogues modulate MUFAs metabolism to improve ferroptosis and aging by direct targeting of ACSL3.Acta pharmaceutica Sinica. B · 2026Article
- Systematic Optimization of Proteolysis-Targeting Chimeras for PIN1 Enables Selective Degradation and Antitumor Activity In Vivo.Pharmaceutics · 2026Article
- Prolyl-isomerase Pin1 drives platinum resistance by regulating Notch3 stability and function in ovarian cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- Pleiotropic effects of all-trans retinoic acid in attenuating the hallmarks of colorectal cancer- challenges and scope of differentiation therapy.Cancer gene therapy · 2026Review
- Scaffold Hopping and Optimization of Thiazole Hybrids as Selective PIN1 Inhibitors: A Computational Study.Medicinal chemistry (Shariqah (United Arab Emirates)) · 2026Article
- Self-synergizing mutual prodrug liposomes for targeted cancer therapyTheranostics · 2026Article
- Dual-site spatiotemporal and simultaneous inhibition on PIN1 via arsenic-retinoic albumin nanoparticles enables synergistic oncotherapy.Journal of nanobiotechnology · 2025Article
- The Prolyl Isomerase PIN1 Affects Fibroblast Differentiation States and Cross-talk in Pancreatic Cancer.Cancer research · 2025Article
- Vitamins A and D and Their Combinations for Breast and Colorectal Cancers: Analysis of the Clinical, Epidemiological, Preclinical and Transcriptomic Data.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Dual-Targeted Nanovesicles Induced Cancer Stem-Like Cell Differentiation to Sensitize Hepatocellular Carcinoma Radiotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Covalent Inhibition of the Peptidyl-Prolyl Isomerase Pin1 by Sulfopin Results in a Broad Impact on the Phosphoproteome of Human Osteosarcoma U2-OS Cells.Proteomics · 2025Article
- Temperature-sensitive sodium beta-glycerophosphate/chitosan hydrogel loaded with all-trans retinoic acid regulates Pin1 to inhibit the formation of spinal cord injury-induced rat glial scar.Bioengineering & translational medicine · 2025Article
- HEX-1 reduces colitis-driven colorectal cancer via inactivating the prolyl isomerase PIN1 sensitization and remodeling the gut microbiota.Discover oncology · 2025Article
- PIN1-SUMO2/3 motif suppresses excessive RNF168 chromatin accumulation and ubiquitin signaling to promote IR resistance.Nature communications · 2025Article
- PIN1 Prolyl Isomerase Promotes Initiation and Progression of Bladder Cancer through the SREBP2-Mediated Cholesterol Biosynthesis Pathway.Cancer discovery · 2025Article
- Overexpression of Pin1 regulated by TOP2A, which subsequently stabilizes Pyk2 to promote bortezomib resistance in multiple myeloma.Cancer gene therapy · 2025Article
100 more citing papers are in PubMed but not listed here.
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Authors and funding
25 authors at 6 institutions in 2 countries.
Shuo Wei1] Division of Translational Therapeutics, Department of Medicine, Beth Israel Deaconess Medical Center (BIDMC), Harvard Medical School, Boston, Massachusetts, USA. [2] Department of Medicine, BIDMC, Harvard Medical School, Boston, Massachusetts, USA.. [3] Cancer Research Institute, Beth Israel Deaconess Cancer Center, Harvard Medical School, Boston, Massachusetts, USA.
Shingo Kozono1] Division of Translational Therapeutics, Department of Medicine, Beth Israel Deaconess Medical Center (BIDMC), Harvard Medical School, Boston, Massachusetts, USA. [2] Department of Medicine, BIDMC, Harvard Medical School, Boston, Massachusetts, USA.. [3] Cancer Research Institute, Beth Israel Deaconess Cancer Center, Harvard Medical School, Boston, Massachusetts, USA.
Lev Kats1] Department of Medicine, BIDMC, Harvard Medical School, Boston, Massachusetts, USA.. [2] Cancer Research Institute, Beth Israel Deaconess Cancer Center, Harvard Medical School, Boston, Massachusetts, USA. [3] Department of Pathology, BIDMC, Harvard Medical School, Boston, Massachusetts, USA.
Morris Nechama1] Division of Translational Therapeutics, Department of Medicine, Beth Israel Deaconess Medical Center (BIDMC), Harvard Medical School, Boston, Massachusetts, USA. [2] Department of Medicine, BIDMC, Harvard Medical School, Boston, Massachusetts, USA.. [3] Cancer Research Institute, Beth Israel Deaconess Cancer Center, Harvard Medical School, Boston, Massachusetts, USA.
Wenzong LiDepartment of Molecular Biosciences, University of Texas, Austin, Texas, USA.
Jlenia Guarnerio1] Department of Medicine, BIDMC, Harvard Medical School, Boston, Massachusetts, USA.. [2] Cancer Research Institute, Beth Israel Deaconess Cancer Center, Harvard Medical School, Boston, Massachusetts, USA. [3] Department of Pathology, BIDMC, Harvard Medical School, Boston, Massachusetts, USA.
Manli Luo1] Division of Translational Therapeutics, Department of Medicine, Beth Israel Deaconess Medical Center (BIDMC), Harvard Medical School, Boston, Massachusetts, USA. [2] Department of Medicine, BIDMC, Harvard Medical School, Boston, Massachusetts, USA.. [3] Cancer Research Institute, Beth Israel Deaconess Cancer Center, Harvard Medical School, Boston, Massachusetts, USA.
Mi-Hyeon YouDivision of Gerontology, Department of Medicine, BIDMC, Harvard Medical School, Boston, Massachusetts, USA.
Yandan Yao1] Division of Translational Therapeutics, Department of Medicine, Beth Israel Deaconess Medical Center (BIDMC), Harvard Medical School, Boston, Massachusetts, USA. [2] Department of Medicine, BIDMC, Harvard Medical School, Boston, Massachusetts, USA.. [3] Cancer Research Institute, Beth Israel Deaconess Cancer Center, Harvard Medical School, Boston, Massachusetts, USA.
Asami Kondo1] Division of Translational Therapeutics, Department of Medicine, Beth Israel Deaconess Medical Center (BIDMC), Harvard Medical School, Boston, Massachusetts, USA. [2] Department of Medicine, BIDMC, Harvard Medical School, Boston, Massachusetts, USA.. [3] Cancer Research Institute, Beth Israel Deaconess Cancer Center, Harvard Medical School, Boston, Massachusetts, USA.
Hai Hu1] Department of Medicine, BIDMC, Harvard Medical School, Boston, Massachusetts, USA.. [2] Cancer Research Institute, Beth Israel Deaconess Cancer Center, Harvard Medical School, Boston, Massachusetts, USA.
Gunes BozkurtDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA.
Nathan J MoerkeDepartment of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA.
Shugeng CaoDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA.
Markus Reschke1] Department of Medicine, BIDMC, Harvard Medical School, Boston, Massachusetts, USA.. [2] Cancer Research Institute, Beth Israel Deaconess Cancer Center, Harvard Medical School, Boston, Massachusetts, USA. [3] Department of Pathology, BIDMC, Harvard Medical School, Boston, Massachusetts, USA.
Chun-Hau Chen1] Division of Translational Therapeutics, Department of Medicine, Beth Israel Deaconess Medical Center (BIDMC), Harvard Medical School, Boston, Massachusetts, USA. [2] Department of Medicine, BIDMC, Harvard Medical School, Boston, Massachusetts, USA.. [3] Cancer Research Institute, Beth Israel Deaconess Cancer Center, Harvard Medical School, Boston, Massachusetts, USA.
Eduardo M RegoDepartment of Internal Medicine, University of São Paulo, Ribeirão Preto, Brazil.
Francesco Lo-CocoDepartment of Biomedicine and Prevention, Tor Vergata University and Santa Lucia Foundation, Rome, Italy.
Lewis C Cantley1] Department of Medicine, BIDMC, Harvard Medical School, Boston, Massachusetts, USA.. [2] Cancer Research Institute, Beth Israel Deaconess Cancer Center, Harvard Medical School, Boston, Massachusetts, USA. [3] Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA.
Tae Ho LeeDivision of Gerontology, Department of Medicine, BIDMC, Harvard Medical School, Boston, Massachusetts, USA.
Hao WuDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA.
Yan ZhangDepartment of Molecular Biosciences, University of Texas, Austin, Texas, USA.
Pier Paolo Pandolfi1] Department of Medicine, BIDMC, Harvard Medical School, Boston, Massachusetts, USA.. [2] Cancer Research Institute, Beth Israel Deaconess Cancer Center, Harvard Medical School, Boston, Massachusetts, USA. [3] Department of Pathology, BIDMC, Harvard Medical School, Boston, Massachusetts, USA.
Xiao Zhen Zhou1] Division of Translational Therapeutics, Department of Medicine, Beth Israel Deaconess Medical Center (BIDMC), Harvard Medical School, Boston, Massachusetts, USA. [2] Department of Medicine, BIDMC, Harvard Medical School, Boston, Massachusetts, USA.. [3] Cancer Research Institute, Beth Israel Deaconess Cancer Center, Harvard Medical School, Boston, Massachusetts, USA.
Kun Ping Lu1] Division of Translational Therapeutics, Department of Medicine, Beth Israel Deaconess Medical Center (BIDMC), Harvard Medical School, Boston, Massachusetts, USA. [2] Department of Medicine, BIDMC, Harvard Medical School, Boston, Massachusetts, USA.. [3] Cancer Research Institute, Beth Israel Deaconess Cancer Center, Harvard Medical School, Boston, Massachusetts, USA.
Beth Israel Deaconess Medical Center · USHarvard University · USThe University of Texas at Austin · USBeth Israel Deaconess Hospital · USTranslational Therapeutics (United States) · USUniversidade de São Paulo · BR
Funding
Structural & Functional Studies of TLR/IL-1R SignalingR37AI050872 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI WU, HAO · 2012 to 2021
$4.7MRole of the Prolyl Isomerase Pin1 in the Development and Treatment of AsthmaR01HL111430 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI LU, KUN PING · 2012 to 2015
$2.7MGene-specific transcriptional silencing directed by dephosphorylation of RNAP IIR01GM104896 · NIGMS · UNIVERSITY OF TEXAS AT AUSTIN · PI ZHANG, YAN JESSIE · 2013 to 2022
$2.4MFunction and Regulation of the Phosphorylation-Specific Prolyl Isomerase Pin1R01CA167677 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI LU, KUN PING · 2012 to 2016
$1.9MIdentification of Pin1 Chemical Probes for Studying Phosphorylation SignalingR03DA031663 · NIDA · BETH ISRAEL DEACONESS MEDICAL CENTER · PI LU, KUN PING · 2011 to 2012
$87kNCI NIH HHS R01 CA167677NCI NIH HHS R01CA167677NHLBI NIH HHS R01 HL111430NHLBI NIH HHS R01HL111430NIAID NIH HHS R37 AI050872NIDA NIH HHS R03 DA031663NIDA NIH HHS R03DA031663NIGMS NIH HHS R01 GM104896
Abstract
A common key regulator of oncogenic signaling pathways in multiple tumor types is the unique isomerase Pin1. However, available Pin1 inhibitors lack the required specificity and potency for inhibiting Pin1 function in vivo. By using mechanism-based screening, here we find that all-trans retinoic acid (ATRA)--a therapy for acute promyelocytic leukemia (APL) that is considered the first example of targeted therapy in cancer, but whose drug target remains elusive--inhibits and degrades active Pin1 selectively in cancer cells by directly binding to the substrate phosphate- and proline-binding pockets in the Pin1 active site. ATRA-induced Pin1 ablation degrades the protein encoded by the fusion oncogene PML-RARA and treats APL in APL cell and animal models as well as in human patients. ATRA-induced Pin1 ablation also potently inhibits triple-negative breast cancer cell growth in human cells and in animal models by acting on many Pin1 substrate oncogenes and tumor suppressors. Thus, ATRA simultaneously blocks multiple Pin1-regulated cancer-driving pathways, an attractive property for treating aggressive and drug-resistant tumors.
Indexed as
Gene Expression Regulation, LeukemicGene Expression Regulation, NeoplasticAnimalsAntineoplastic AgentsBreast NeoplasmsCatalysisCatalytic DomainCell Line, TumorDose-Response Relationship, DrugFemaleFibroblastsHEK293 CellsHumansLeukemia, Promyelocytic, AcuteMCF-7 CellsMiceAntineoplastic AgentsNIMA-Interacting Peptidylprolyl IsomerasePeptidylprolyl IsomerasePhosphatesPIN1 protein, humanPin1 protein, mouseProlineTretinoin
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