Kinome-wide shRNA Screen Identifies the Receptor Tyrosine Kinase AXL as a Key Regulator for Mesenchymal Glioblastoma Stem-like Cells

摘要: Glioblastoma is a highly lethal cancer for which novel therapeutics are urgently needed. Two distinct subtypes of glioblastoma stem-like cells (GSCs) were recently identified: mesenchymal (MES) and proneural (PN). To identify mechanisms to target the more aggressive MES GSCs, we combined transcriptomic expression analysis kinome-wide short hairpin RNA screening PN GSCs. In comparison found significant upregulation phosphorylation receptor tyrosine kinase AXL in Knockdown significantly decreased GSC self-renewal capacity vitro inhibited growth patient-derived xenografts. Moreover, inhibition with shRNA or pharmacologic inhibitors also increased cell death Clinically, was elevated GBM subtype correlated poor prognosis multiple cancers. conclusion, identified as potential molecular approaches treat other solid