Targeting RPL39 and MLF2 reduces tumor initiation and metastasis in breast cancer by inhibiting nitric oxide synthase signaling Academic Article uri icon

Overview

MeSH Major

  • Breast Neoplasms
  • Lung Neoplasms
  • Neoplastic Stem Cells
  • Nitric Oxide Synthase
  • Nuclear Proteins
  • Ribosomal Proteins

abstract

  • We previously described a gene signature for breast cancer stem cells (BCSCs) derived from patient biopsies. Selective shRNA knockdown identified ribosomal protein L39 (RPL39) and myeloid leukemia factor 2 (MLF2) as the top candidates that affect BCSC self-renewal. Knockdown of RPL39 and MLF2 by specific siRNA nanoparticles in patient-derived and human cancer xenografts reduced tumor volume and lung metastases with a concomitant decrease in BCSCs. RNA deep sequencing identified damaging mutations in both genes. These mutations were confirmed in patient lung metastases (n = 53) and were statistically associated with shorter median time to pulmonary metastasis. Both genes affect the nitric oxide synthase pathway and are altered by hypoxia. These findings support that extensive tumor heterogeneity exists within primary cancers; distinct subpopulations associated with stem-like properties have increased metastatic potential.

publication date

  • January 2014

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4066479

Digital Object Identifier (DOI)

  • 10.1073/pnas.1320769111

PubMed ID

  • 24876273

Additional Document Info

start page

  • 8838

end page

  • 43

volume

  • 111

number

  • 24