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

eLife | 2014

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.

Pubmed ID: 24898756 RIS Download

Research resources used in this publication

None found

Antibodies used in this publication

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Associated grants

  • Agency: NINDS NIH HHS, United States
    Id: R01 NS081706
  • Agency: Howard Hughes Medical Institute, United States
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS034389
  • Agency: NCI NIH HHS, United States
    Id: P30 CA008748
  • Agency: Medical Research Council, United Kingdom
    Id: MC_UU_12022/7
  • Agency: Medical Research Council, United Kingdom
    Id: MC_UP_1101/4

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COSMIC - Catalogue Of Somatic Mutations In Cancer (tool)

RRID:SCR_002260

Database to store and display somatic mutation information and related details and contains information relating to human cancers. The mutation data and associated information is extracted from the primary literature. In order to provide a consistent view of the data a histology and tissue ontology has been created and all mutations are mapped to a single version of each gene. The data can be queried by tissue, histology or gene and displayed as a graph, as a table or exported in various formats.
Some key features of COSMIC are:
* Contains information on publications, samples and mutations. Includes samples which have been found to be negative for mutations during screening therefore enabling frequency data to be calculated for mutations in different genes in different cancer types.
* Samples entered include benign neoplasms and other benign proliferations, in situ and invasive tumours, recurrences, metastases and cancer cell lines.

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RRID:SCR_007303

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RRID:CVCL_1259

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