Unknown,Transcriptomics,Genomics,Proteomics

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The RNA-binding protein RBM47 suppresses metastatic breast cancer progression

ABSTRACT: 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 have identified RNA binding motif protein 47 (RBM47) as a candidate suppressor of breast cancer metastasis. RBM47 inhibited breast cancer progression in experimental models. Transcriptome-wide analysis of RBM47 localization by HITS-CLIP revealed widespread binding to mRNAs, preferentially at the 3' UTRs. RBM47 altered the abundance of a subset of its target mRNAs. Some of the mRNAs stabilized by RBM47, as exemplified by dickkopf WNT signaling pathway inhibitor 1 (DKK1), mediate tumor suppressive effects downstream of RBM47. This work identifies RBM47 as a suppressor of breast cancer progression and highlights the potential of global RNA modulatory events as a source of metastasis-promoting phenotypic traits. Cancer cells transduced with doxycycline-inducible wildtype RBM47 or the RBM47-I281fs mutant, treated with increasing concentrations of doxycycline.

ORGANISM(S): Homo sapiens

SUBMITTER: Sakari Vanharanta 

PROVIDER: E-GEOD-53779 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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

Vanharanta Sakari S   Marney Christina B CB   Shu Weiping W   Valiente Manuel M   Zou Yilong Y   Mele Aldo A   Darnell Robert B RB   Massagué Joan J  

eLife 20140604

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 experimenta  ...[more]

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