Loss of the multifunctional RNA-binding protein RBM47 as a source of selectable metastatic traits in breast cancer

Elife. 2014 Jun 4;3:e02734. doi: 10.7554/eLife.02734.


The mechanisms through which cancer cells lock in altered transcriptional programs in support of metastasis remain largely unknown. Through integrative analysis of clinical breast cancer gene expression datasets, cell line models of breast cancer progression, and mutation data from cancer genome resequencing studies, we identified RNA binding motif protein 47 (RBM47) as a suppressor of breast cancer progression and metastasis. RBM47 inhibited breast cancer re-initiation and growth in experimental models. Transcriptome-wide HITS-CLIP analysis revealed widespread RBM47 binding to mRNAs, most prominently in introns and 3'UTRs. RBM47 altered splicing and abundance of a subset of its target mRNAs. Some of the mRNAs stabilized by RBM47, as exemplified by dickkopf WNT signaling pathway inhibitor 1, inhibit tumor progression downstream of RBM47. Our work identifies RBM47 as an RNA-binding protein that can suppress breast cancer progression and demonstrates how the inactivation of a broadly targeted RNA chaperone enables selection of a pro-metastatic state.

Keywords: RNA binding proteins; breast cancer; chromosomes; genes; human; human biology; medicine; metastasis; mouse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Alternative Splicing
  • Amino Acid Motifs
  • Animals
  • Binding Sites
  • Brain Neoplasms / secondary
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Introns
  • Mice
  • Mice, Nude
  • Neoplasm Metastasis
  • RNA Interference
  • RNA-Binding Proteins / metabolism*
  • Transcription, Genetic
  • Transcriptome
  • Wnt Proteins / metabolism


  • 3' Untranslated Regions
  • RBM47 protein, human
  • RNA-Binding Proteins
  • Rbm47 protein, mouse
  • Wnt Proteins

Associated data

  • GEO/GSE53779
  • GEO/GSE58381