Alternative splicing and cancer metastasis: prognostic and therapeutic applications

Metastatic cells exhibit an extraordinary phenotypic plasticity, not only in adapting to unfamiliar microenvironments but also in surviving aggressive treatments and immune responses. A major source of phenotypic variability is alternative splicing (AS) of the pre-messenger RNA. This process is catalyzed by one of the most complex pieces of cellular molecular regulatory events, the spliceosome, which is composed of ribonucleoproteins and polypeptides termed spliceosome factors. With strong evidence indicating that AS affects nearly all genes encoded by the human genome, aberrant AS programs have a significant impact on cancer cell development and progression. In this review, we present insights about the genomic and epigenomic factors affecting AS, summarize the most recent findings linking aberrant AS to metastatic progression, and highlight potential prognostic and therapeutic applications.