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Series GSE57243 Query DataSets for GSE57243
Status Public on Jun 03, 2014
Title Cell-type restricted activity of hnRNPM promotes breast cancer metastasis via regulating alternative splicing
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary 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
Contributor(s) Xinshu X, Chonghui C
Citation(s) 24840202
Submission date May 01, 2014
Last update date May 15, 2019
Contact name Chonghui Cheng
Phone 3125035248
Organization name Northwestern University
Department Hematology/Oncology Division, Feinberg School of Medicine
Lab Chonghui Cheng
Street address 303 E Superior Street, Robert H. Lurie Comprehensive Cancer Center 5-119
City Chicago
State/province IL
ZIP/Postal code 60611
Country USA
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (4)
GSM1385885 hnRNPM KD_rep1
GSM1385886 hnRNPM KD_rep2
GSM1385887 Control_rep1
BioProject PRJNA247397
SRA SRP041962

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Supplementary file Size Download File type/resource
GSE57243_control_and_hnRNPM.rpkm.txt.txt.gz 516.7 Kb (ftp)(http) TXT
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