GSE139074 AKAP8 inhibits tumor metastasis by antagonizing EMT-associated RNA alternative splicing

Contributors : Chonghui Cheng ; Samuel E Harvey ; Rong ZhengSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensTumor metastasis is the most lethal attribute of breast cancer, and the epithelial-mesenchymal  transition (EMT) plays an important role in this process. Alternative splicing has been shown to causally contribute to EMT; however, the scope of critical splicing events and the regulatory network of splicing factors that govern them remain largely unexplored. Here we report the identification o f A-Kinase Anchor Protein (AKAP8) as an EMT splicing regulatory factor that impedes EMT and breast cancer metastasis. AKAP8 not only is capable of inhibiting splicing activity of the EMT-promoting splicing regulator hnRNPM through protein-protein interaction, it also binds to RNA directly and al ters splicing outcomes. Genome-wide analysis revealed that AKAP8-mediated splicing events, specifically in epithelial cells, are reversely regulated during EMT, suggesting that AKAP8 maintains an epithelial cell-state splicing program. Experimental manipulation of a newly identified AKAP8 splicing target calsyntenin-1 (CLSTN1) revealed that splice isoform switching of CLSTN1 is crucial for EMT. Mining breast cancer patient data supports the experimental findings and AKAP8 expression and the alternative splicing of CLSTN1 predict patient survival. Our work demonstrates the essential ity of RNA metabolism that impinges on metastatic br...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research