Lay summary
Cancer cells are continuously evolving under selective pressure by increasing their protein repertoire. This feature of cancer cells is driven by their ability to generate new RNA species via alternative splicing (AS) in combination with relaxing the quality control mechanism called nonsense-mediated mRNA decay (NMD). However, how cancer cells manipulate AS and NMD remains poorly understood. Our study will use cutting-edge gene editing CRISPR-Cas9 technology coupled with long read RNA-sequencing to gain critical insight into how cancer cells exploit AS and NMD to express aberrantly spliced transcripts capable of driving cancer evolution, metastasis and treatment resistance.