Report

Deregulation of ribosomal protein expression and translation promotes breast cancer metastasis

See allHide authors and affiliations

Science  27 Mar 2020:
Vol. 367, Issue 6485, pp. 1468-1473
DOI: 10.1126/science.aay0939

You are currently viewing the abstract.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

Metastasis: A matter of translation?

Solid tumors shed a small number of cancer cells into the bloodstream, some of which are believed to contribute to metastasis. The molecular features that confer these circulating tumor cells (CTCs) with metastatic potential are poorly understood. Ebright et al. studied CTCs from breast cancer patients and found that cells with increased expression levels of certain ribosomal proteins and regulators of translation had greater metastatic capacity in a mouse model (see the Perspective by Ma and Jeffrey). Consistent with this finding, patients with higher levels of this subset of CTCs tended to have a poorer prognosis.

Science, this issue p. 1468; see also p. 1424

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.

View Full Text

Stay Connected to Science


Editor's Blog