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Updated: Oct 29, 2025

A Semi-Quantitative Drug Affinity Responsive Target Stability DARTS assay for studying Rapamycin/mTOR interaction
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A Semi-Quantitative Drug Affinity Responsive Target Stability DARTS assay for studying Rapamycin/mTOR interaction

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Daptomycin suppresses tumor migration and angiogenesis via binding to ribosomal protein S19 in humans

Sung Min Cho1, Hwa Jung Lee1, Peter Karuso2

  • 1Chemical Genomics Global Research Laboratory, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea.

The Journal of Antibiotics
|July 13, 2021
PubMed

Insights

Daptomycin (DAP) reduces cancer cell proliferation by targeting ribosomal protein S19 (RPS19), an extraribosomal protein. This interaction suppresses vascular endothelial growth factor (VEGF) secretion, inhibiting cancer cell migration.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Daptomycin (DAP), an antibiotic, demonstrates selective anti-cancer activity against MCF7 breast cancer cells.
  • Previous research indicated DAP binds to human ribosomal protein S19 (RPS19).

Purpose of the Study:

  • To investigate the role of RPS19 in DAP's anti-cancer effects.
  • To elucidate the mechanism underlying DAP's anti-cancer activity.

Main Methods:

  • Cell proliferation assays
  • Western blotting
  • siRNA knockdown of RPS19
  • CETSA and ITDRFCETSA assays
  • VEGF secretion assays

Main Results:

  • DAP reduces cancer cell proliferation but does not induce autophagy, apoptosis, or affect cell viability.
  • RPS19 regulates vascular endothelial growth factor (VEGF) secretion, but not EGF, PDGF, or FGF.
  • siRNA-mediated knockdown of RPS19 enhanced DAP's potency.
  • DAP suppressed VEGF secretion and inhibited cancer cell migration.

Conclusions:

  • DAP exhibits anti-cancer activity through an extraribosomal function of RPS19, involving VEGF regulation.
  • RPS19 is a potential therapeutic target for novel anti-cancer drug development.

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