ArticleNature genetics2017
Functional screen of MSI2 interactors identifies an essential role for SYNCRIP in myeloid leukemia stem cells.
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Article in Nature genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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72citing papers in PubMed
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Who cites it
72 citing papers in PubMed, 106 citations in OpenAlex.
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12 more citing papers are in PubMed but not listed here.
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Authors and funding
43 authors at 11 institutions in 3 countries.
Ly P VuMolecular Pharmacology Program, Center for Cell Engineering, Center for Stem Cell Biology, and Center for Experimental Therapeutics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Camila PrietoMolecular Pharmacology Program, Center for Cell Engineering, Center for Stem Cell Biology, and Center for Experimental Therapeutics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Elianna M AminMolecular Pharmacology Program, Center for Cell Engineering, Center for Stem Cell Biology, and Center for Experimental Therapeutics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Sagar ChhangawalaPhysiology, Biophysics and Systems Biology Graduate Program, Weill Cornell Graduate School of Medical Sciences, Cornell University, New York, New York, USA.ORCID http://orcid.org/0000-0001-9626-1034
Andrei KrivtsovCancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
M Nieves Calvo-VidalDepartment of Medicine, Division of Hematology/Oncology, Weill Cornell Medical College, New York, New York, USA.
Timothy ChouMolecular Pharmacology Program, Center for Cell Engineering, Center for Stem Cell Biology, and Center for Experimental Therapeutics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Arthur ChowMolecular Pharmacology Program, Center for Cell Engineering, Center for Stem Cell Biology, and Center for Experimental Therapeutics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Gerard MinuesaMolecular Pharmacology Program, Center for Cell Engineering, Center for Stem Cell Biology, and Center for Experimental Therapeutics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Sun Mi ParkMolecular Pharmacology Program, Center for Cell Engineering, Center for Stem Cell Biology, and Center for Experimental Therapeutics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Trevor S BarloweMolecular Pharmacology Program, Center for Cell Engineering, Center for Stem Cell Biology, and Center for Experimental Therapeutics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
James TaggartMolecular Pharmacology Program, Center for Cell Engineering, Center for Stem Cell Biology, and Center for Experimental Therapeutics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Patrick TivnanMolecular Pharmacology Program, Center for Cell Engineering, Center for Stem Cell Biology, and Center for Experimental Therapeutics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Raquel P DeeringHarvard Medical School, Boston, Massachusetts, USA.
Lisa P ChuDivision of Hematology, Brigham and Woman's Hospital, Boston, Massachusetts, USA.
Jeong-Ah KwonWhitehead Institute, Boston, Massachusetts, USA.
Cem MeydanInstitute for Computational Biomedicine, Department of Physiology and Biophysics, Weill Cornell Medical College, New York, New York, USA.
Javier Perales-PatonTranslational Bioinformatics Unit, Clinical Research Programme, Spanish National Cancer Research Centre, Madrid, Spain.ORCID http://orcid.org/0000-0003-0780-6683
Arora ArshiDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Mithat GönenDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Christopher FamulareHuman Oncology and Pathogenesis Program, Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Minal PatelHuman Oncology and Pathogenesis Program, Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Elisabeth PaiettaDepartment of Medicine, Montefiore Medical Center, Bronx, New York, USA.
Martin S TallmanLeukemia Service, Department of Medicine, Memorial Sloan Kettering Hospital, New York, New York, USA.
Yuheng LuComputational Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Jacob GlassLeukemia Service, Department of Medicine, Memorial Sloan Kettering Hospital, New York, New York, USA.ORCID http://orcid.org/0000-0003-0363-7763
Francine E Garret-BakelmanDepartment of Medicine and Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia, USA.
Ari MelnickDivision of Hematology and Medical Oncology, Departments of Medicine and Pharmacology, Weill Cornell Medical College, Cornell University, New York, New York, USA.
Ross LevineHuman Oncology and Pathogenesis Program, Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Fatima Al-ShahrourTranslational Bioinformatics Unit, Clinical Research Programme, Spanish National Cancer Research Centre, Madrid, Spain.
Marcus JäråsDepartment of Clinical Genetics, Lund University, Lund, Sweden.
Nir HacohenHarvard Medical School, Boston, Massachusetts, USA.
Alexia HwangRNAi Core, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Ralph GarippaRNAi Core, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Christopher J LengnerDepartment of Animal Biology, Department of Cell and Developmental Biology, and Institute for Regenerative Medicine, Schools of Veterinary Medicine and Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Scott A ArmstrongCancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Leandro CerchiettiDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
Glenn S CowleyDiscovery Sciences, Janssen Research and Development, Spring House, Pennsylvania, USA.
David RootBroad Institute, Boston, Massachusetts, USA.
John DoenchBroad Institute, Boston, Massachusetts, USA.ORCID http://orcid.org/0000-0002-3707-9889
Christina LeslieComputational Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Benjamin L EbertDivision of Hematology, Brigham and Woman's Hospital, Boston, Massachusetts, USA.
Michael G KharasMolecular Pharmacology Program, Center for Cell Engineering, Center for Stem Cell Biology, and Center for Experimental Therapeutics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.ORCID http://orcid.org/0000-0002-1165-6991
Memorial Sloan Kettering Cancer Center · USCornell University · USHarvard University · USBroad Institute · USSpanish National Cancer Research Centre · ESWoman's Hospital · USCalifornia Institute for Regenerative Medicine · USJanssen (United States) · USLund University · SEMontefiore Medical Center · USWhitehead Institute for Biomedical Research · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4MTranslational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Eric Collisson · 1985 to 2026
$296.4MECOG-ACRIN Biospecimen Bank to Support NCTNU24CA196172 · NCI · ECOG-ACRIN MEDICAL RESEARCH FOUNDATION · PI STANLEY R. HAMILTON, Scott D Jewell · 2015 to 2026
$41.1MECOG Specimen BankingU24CA114737 · NCI · FRONTIER SCI &TECHNOLOGY RSCH FDN, INC · PI COMIS, ROBERT L · 2005 to 2014
$9.3MUncovering the role for MSI2 network in hematopoietic stem cellsR01DK101989 · NIDDK · SLOAN-KETTERING INST CAN RESEARCH · PI Michael Kharas, Vijay Ganesh Sankaran · 2014 to 2026
$6.2MCharacterizing the MSI2 network in leukemiaR01CA193842 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI KHARAS, MICHAEL · 2015 to 2025
$4.1MECOG-ACRIN INTEGRATED LEUKEMIA TRANSLATIONAL RESEARCH CENTERU10CA180827 · NCI · MONTEFIORE MEDICAL CENTER (BRONX, NY) · PI LEVINE, ROSS L, MELNICK, ARI M. · 2014 to 2018
$3.0MMolecular and genetic analysis of novel Slicer-dependent miRNA pathways in bloodR01HL135564 · NHLBI · SLOAN-KETTERING INST CAN RESEARCH · PI KHARAS, MICHAEL, LAI, ERIC C · 2017 to 2020
$2.9MThe role of the Musashi family in hematopoiesisK01DK084261 · NIDDK · SLOAN-KETTERING INST CAN RESEARCH · PI KHARAS, MICHAEL · 2009 to 2013
$784kNCI NIH HHS P30 CA008748NCI NIH HHS P30 CA015704NCI NIH HHS R01 CA193842NCI NIH HHS U10 CA180827NCI NIH HHS U24 CA114737NCI NIH HHS U24 CA196172NHLBI NIH HHS R01 HL135564NIDDK NIH HHS K01 DK084261NIDDK NIH HHS R01 DK101989
Abstract
The identity of the RNA-binding proteins (RBPs) that govern cancer stem cells remains poorly characterized. The MSI2 RBP is a central regulator of translation of cancer stem cell programs. Through proteomic analysis of the MSI2-interacting RBP network and functional shRNA screening, we identified 24 genes required for in vivo leukemia. Syncrip was the most differentially required gene between normal and myeloid leukemia cells. SYNCRIP depletion increased apoptosis and differentiation while delaying leukemogenesis. Gene expression profiling of SYNCRIP-depleted cells demonstrated a loss of the MLL and HOXA9 leukemia stem cell program. SYNCRIP and MSI2 interact indirectly though shared mRNA targets. SYNCRIP maintains HOXA9 translation, and MSI2 or HOXA9 overexpression rescued the effects of SYNCRIP depletion. Altogether, our data identify SYNCRIP as a new RBP that controls the myeloid leukemia stem cell program. We propose that targeting these RBP complexes might provide a novel therapeutic strategy in leukemia.
Indexed as
Gene Expression Regulation, LeukemicAnimalsCell SurvivalFemaleHematopoiesisHeterogeneous-Nuclear RibonucleoproteinsHomeodomain ProteinsHumansLeukemia, Biphenotypic, AcuteLeukemia, MyeloidMice, Inbred C57BLMice, KnockoutMyeloid Progenitor CellsRNA-Binding ProteinsRNA, Small InterferingXenograft Model Antitumor AssaysHeterogeneous-Nuclear Ribonucleoproteinshomeobox protein HOXA9Homeodomain ProteinsMSI2 protein, humanRNA-Binding ProteinsRNA, Small InterferingSYNCRIP protein, humanSyncrip protein, mouse
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