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SRP041962
Homo sapiens
4 Downloadable Samples
IlluminaGenomeAnalyzer
Description
Tumor metastasis remains the major cause of cancer-related death, but its molecular basis is still not well understood. Here we uncovered a splicing-mediated pathway that is essential for breast cancer metastasis. We show that the RNA-binding protein hnRNPM promotes breast cancer metastasis by activating the switch of alternative splicing that occurs during epithelial-mesenchymal transition (EMT). Genome-wide deep sequencing analysis suggests that hnRNPM potentiates TGFb signaling and identifies CD44 as a key downstream target of hnRNPM. hnRNPM ablation prevents TGFb-induced EMT and inhibits breast cancer metastasis in mice, whereas enforced expression of the specific CD44s splice isoform overrides the loss of hnRNPM and permits EMT and metastasis. Mechanistically, we demonstrate that the ubiquitously expressed hnRNPM acts in a mesenchymal-specific manner to precisely control CD44 splice isoform switching during EMT. This restricted cell-type activity of hnRNPM is achieved by competition with ESRP1, an epithelial-splicing regulator that binds to the same cis-regulatory RNA elements and is repressed during EMT. Importantly, hnRNPM is associated with aggressive breast cancer and correlates with increased CD44s in patient specimens. These findings demonstrate a novel molecular mechanism through which tumor metastasis is endowed by the hnRNPM-mediated splicing program. Overall design: RNAseq for control, hnRNPM siRNA treated lung metastatic LM2 clonal line, derived from the mesenchymal MDA-MB-231 cells
Publication Title
Cell type-restricted activity of hnRNPM promotes breast cancer metastasis via regulating alternative splicing.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 15 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
These experiments aim determine the effects of Smo and Ets-2 signaling on fibroblast gene expression.
Publication Title
Genetic ablation of Smoothened in pancreatic fibroblasts increases acinar-ductal metaplasia.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The goal of this study was to investigate the transcriptional regulation in cells grown on Fibronectin when compared to Collagen I
Publication Title
Loss of fibronectin from the aged stem cell niche affects the regenerative capacity of skeletal muscle in mice.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples