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


Authors: Vanharanta, S.; Marney, C. B.; Shu, W.; Valiente, M.; Zou, Y.; Mele, A.; Darnell, R. B.; Massagué, J.
Article Title: Loss of the multifunctional RNA-binding protein RBM47 as a source of selectable metastatic traits in breast cancer
Abstract: 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. © Vanharanta et al.
Journal Title: eLife
Volume: 2014
Issue: 3
ISSN: 2050-084X
Publisher: eLife Sciences Publications Ltd.  
Date Published: 2014-06-01
Start Page: e02734
Language: English
DOI: 10.7554/eLife.02734
PROVIDER: scopus
PMCID: PMC4073284
PUBMED: 24898756
DOI/URL:
Notes: Export Date: 1 August 2014 -- Source: Scopus
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  1. Joan Massague
    388 Massague
  2. Weiping Shu
    18 Shu
  3. Yilong Zou
    15 Zou