Your browser doesn't support javascript.
loading
Inhibition of YTHDF2 triggers proteotoxic cell death in MYC-driven breast cancer.
Einstein, Jaclyn M; Perelis, Mark; Chaim, Isaac A; Meena, Jitendra K; Nussbacher, Julia K; Tankka, Alexandra T; Yee, Brian A; Li, Heyuan; Madrigal, Assael A; Neill, Nicholas J; Shankar, Archana; Tyagi, Siddhartha; Westbrook, Thomas F; Yeo, Gene W.
Afiliación
  • Einstein JM; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA; Stem Cell Program, University of California, San Diego, La Jolla, CA, USA; Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Perelis M; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA; Stem Cell Program, University of California, San Diego, La Jolla, CA, USA; Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Chaim IA; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA; Stem Cell Program, University of California, San Diego, La Jolla, CA, USA; Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Meena JK; Verna & Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Nussbacher JK; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA; Stem Cell Program, University of California, San Diego, La Jolla, CA, USA; Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Tankka AT; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA; Stem Cell Program, University of California, San Diego, La Jolla, CA, USA; Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Yee BA; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA; Stem Cell Program, University of California, San Diego, La Jolla, CA, USA; Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Li H; Verna & Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Madrigal AA; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA; Stem Cell Program, University of California, San Diego, La Jolla, CA, USA; Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Neill NJ; Verna & Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Shankar A; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA; Stem Cell Program, University of California, San Diego, La Jolla, CA, USA; Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Tyagi S; Verna & Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Westbrook TF; Verna & Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Therapeutic Innovation Center (THINC), Baylor College of Medicine, Houston, T
  • Yeo GW; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA; Stem Cell Program, University of California, San Diego, La Jolla, CA, USA; Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA, USA. Electronic address: geneyeo@ucsd.e
Mol Cell ; 81(15): 3048-3064.e9, 2021 08 05.
Article en En | MEDLINE | ID: mdl-34216543
ABSTRACT
RNA-binding proteins (RBPs) are critical regulators of post-transcriptional gene expression, and aberrant RBP-RNA interactions can promote cancer progression. Here, we interrogate the function of RBPs in cancer using pooled CRISPR-Cas9 screening and identify 57 RBP candidates with distinct roles in supporting MYC-driven oncogenic pathways. We find that disrupting YTHDF2-dependent mRNA degradation triggers apoptosis in triple-negative breast cancer (TNBC) cells and tumors. eCLIP and m6A sequencing reveal that YTHDF2 interacts with mRNAs encoding proteins in the MAPK pathway that, when stabilized, induce epithelial-to-mesenchymal transition and increase global translation rates. scRibo-STAMP profiling of translating mRNAs reveals unique alterations in the translatome of single cells within YTHDF2-depleted solid tumors, which selectively contribute to endoplasmic reticulum stress-induced apoptosis in TNBC cells. Thus, our work highlights the therapeutic potential of RBPs by uncovering a critical role for YTHDF2 in counteracting the global increase of mRNA synthesis in MYC-driven breast cancers.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Proteínas de Unión al ARN Límite: Animals / Female / Humans Idioma: En Revista: Mol Cell Asunto de la revista: BIOLOGIA MOLECULAR Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Proteínas de Unión al ARN Límite: Animals / Female / Humans Idioma: En Revista: Mol Cell Asunto de la revista: BIOLOGIA MOLECULAR Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos