Deregulation of splicing factors and breast cancer development

silipo, marco; gautrey, hannah; tyson-capper, alison;

It is well known that many genes implicated in the development and progression of breast cancer undergo aberrant alternative splicing
events to produce proteins with pro-cancer properties.These changes in alternative splicingcan arise frommutations or single-nucleotide
polymorphisms (SNPs) within the DNA sequences of cancer-related genes, which can strongly affect the activity of splicing factors and
influence the splice site choice. However, it is important to note that absence of mutations is not sufficient to prevent misleading
choices in splice site selection. There is nowincreasing evidence to demonstrate that the expression profile of ten splicing factors (including SRs and hnRNPs) and eight RNA-binding proteins changes in breast cancer cells compared with normal cells. These modifications
strongly influence the alternative splicing pattern of many cancer-related genes despite the absence of any detrimental mutations
within their DNA sequences. Thus, a comprehensive assessment of the splicing factor status in breast cancer is important to provide
insights into the mechanisms that lead to breast cancer development and metastasis. Whilst most studies focus on mutations that affect alternative splicing in cancer-related genes, this review focuses on splicing factors and RNA-binding proteins that are themselves
deregulated in breast cancer and implicated in cancer-related alternative splicing events.