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Deregulation of ribosomal protein expression and translation promotes breast cancer metastasis.
Ebright, Richard Y; Lee, Sooncheol; Wittner, Ben S; Niederhoffer, Kira L; Nicholson, Benjamin T; Bardia, Aditya; Truesdell, Samuel; Wiley, Devon F; Wesley, Benjamin; Li, Selena; Mai, Andy; Aceto, Nicola; Vincent-Jordan, Nicole; Szabolcs, Annamaria; Chirn, Brian; Kreuzer, Johannes; Comaills, Valentine; Kalinich, Mark; Haas, Wilhelm; Ting, David T; Toner, Mehmet; Vasudevan, Shobha; Haber, Daniel A; Maheswaran, Shyamala; Micalizzi, Douglas S.
Afiliação
  • Ebright RY; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
  • Lee S; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
  • Wittner BS; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
  • Niederhoffer KL; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
  • Nicholson BT; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
  • Bardia A; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
  • Truesdell S; Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • Wiley DF; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
  • Wesley B; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
  • Li S; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
  • Mai A; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
  • Aceto N; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
  • Vincent-Jordan N; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
  • Szabolcs A; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
  • Chirn B; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
  • Kreuzer J; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
  • Comaills V; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
  • Kalinich M; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
  • Haas W; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
  • Ting DT; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
  • Toner M; Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • Vasudevan S; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
  • Haber DA; Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • Maheswaran S; Center for Bioengineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • Micalizzi DS; Shriners Hospital for Children, Boston, MA 02114, USA.
Science ; 367(6485): 1468-1473, 2020 03 27.
Article em En | MEDLINE | ID: mdl-32029688
ABSTRACT
Circulating tumor cells (CTCs) are shed into the bloodstream from primary tumors, but only a small subset of these cells generates metastases. We conducted an in vivo genome-wide CRISPR activation screen in CTCs from breast cancer patients to identify genes that promote distant metastasis in mice. Genes coding for ribosomal proteins and regulators of translation were enriched in this screen. Overexpression of RPL15, which encodes a component of the large ribosomal subunit, increased metastatic growth in multiple organs and selectively enhanced translation of other ribosomal proteins and cell cycle regulators. RNA sequencing of freshly isolated CTCs from breast cancer patients revealed a subset with strong ribosome and protein synthesis signatures; these CTCs expressed proliferation and epithelial markers and correlated with poor clinical outcome. Therapies targeting this aggressive subset of CTCs may merit exploration as potential suppressors of metastatic progression.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Ribossômicas / Neoplasias da Mama / Células Neoplásicas Circulantes / Metástase Neoplásica Limite: Animals / Female / Humans Idioma: En Revista: Science Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Ribossômicas / Neoplasias da Mama / Células Neoplásicas Circulantes / Metástase Neoplásica Limite: Animals / Female / Humans Idioma: En Revista: Science Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos