Targeting KRAS4A Splicing through the RBM39/DCAF15 Pathway Inhibits Cancer Stem Cells

The authors demonstrated that coordinated regulation of both isoforms through control of splicing was essential for development of Kras mutant tumors. The minor KRAS4A isoform was enriched in cancer stem-like cells, where it responded to hypoxia, while the major KRAS4B was induced by ER stress.