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Deregulation of ribosomal protein expression and translation promotes breast cancer metastasis
Journal article

Deregulation of ribosomal protein expression and translation promotes breast cancer metastasis

  • Ebright, Richard Y. ORCID Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
  • Lee, Sooncheol Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
  • Wittner, Ben S. ORCID Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
  • Niederhoffer, Kira L. ORCID Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
  • Nicholson, Benjamin T. Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
  • Bardia, Aditya Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • Truesdell, Samuel Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
  • Wiley, Devon F. ORCID Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
  • Wesley, Benjamin Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
  • Li, Selena ORCID Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
  • Mai, Andy ORCID Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
  • Aceto, Nicola Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
  • Vincent-Jordan, Nicole Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
  • Szabolcs, Annamaria ORCID Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
  • Chirn, Brian Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
  • Kreuzer, Johannes ORCID Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
  • Comaills, Valentine ORCID Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
  • Kalinich, Mark ORCID Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
  • Haas, Wilhelm ORCID Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • Ting, David T. ORCID Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • Toner, Mehmet Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • Vasudevan, Shobha ORCID Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • Haber, Daniel A. ORCID Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02114, USA.
  • Maheswaran, Shyamala ORCID Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • Micalizzi, Douglas S. ORCID Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
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  • 2020-2-6
Published in:
  • Science. - American Association for the Advancement of Science (AAAS). - 2020, vol. 367, no. 6485, p. 1468-1473
Multidisciplinary
English 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.
Language
  • English
Open access status
green
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Persistent URL
https://sonar.ch/global/documents/30716
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