Best evidence linking the extracellular factor TGF-β to cancer-associated alternative splicing programs.

Alternative splicing is a mechanism by which several RNA transcripts can be created from one gene. Splicing factors are RNA binding proteins recognizing cis-acting sequences that positively or negatively influence the splicing decision based on their relative position to the splice site and identity. However, few studies have focused on the regulation of splicing factors, and even less on the regulation of alternative splicing from extracellular factors. Transforming growth factor beta 1 (TGF-β) is a well study extracellular factors regulating multiple cancer-associated cell phenotype (apoptosis, epithelial to mesenchymal transition, angiogenesis, differentiation into cancer-associated fibroblasts) in a cell type-dependent manner. Intriguingly, there is examples of alternative splicing variants and/or their regulatory splicing factors influencing each of these hallmarks in vitro. Here, we provide the best evidence suggesting that TGF-β may drive cancer-associated alternative splicing programs.