LAUSR

Significance In this work, we have developed a highly controlled non-tumorigenic human bronchial epithelial cell system expressing four ALK fusions found in NSCLC. Employing RNA-seq and phosphoproteomics, we identify both common and isoform-specific differentially expressed genes and phosphorylated proteins downstream of these four ALK fusions. Further, we show that ALK fusions drive an inflammatory expression signature, resulting in increased Serpin B4 levels that result in inhibition of cytotoxic natural killer cell-induced cell death. Our study identifies a novel cell survival mechanism modulated by Serpin B4 downstream of ALK fusion oncogenes in NSCLC. This finding provides a potential therapeutic axis allowing targeting of the immune response together with ALK TKIs in NSCLC.