摘要：SummaryOncogenic mutations in theEGFRgene account for 15–20% of lung adenocarcinoma (LUAD) cases. However, the mechanism for EGFR driven tumor development and growth is not fully understood. Here, using an mRNA expression profiling-based approach we identified betacellulin (BTC) as one the gene upregulated by oncogenic EGFR in an MAP kinase-dependent manner. BTC protein expression was markedly increased in LUAD patient samples compared to normal lung tissue, with higher expression in EGFR-mutant LUAD.BTCwas sufficient to transform immortalized mouse cells, initiate tumor development in mice, and promote the survival of immortalized human lung epithelial cells. Conversely, knockdown ofBTCinhibited the growth of EGFR-mutant human LUAD cells in culture and their tumor-forming ability in mice. Mechanistically,BTCknockdown resulted in attenuated EGFR signaling and apoptosis induction. Collectively, these results demonstrate a key role of BTC in EGFR-mutant LUAD, with potential therapeutic implications in LUAD and other EGFR-mutant cancers.Graphical abstractDisplay OmittedHighlights•BTC is a transcriptional target of oncogenic EGFR•BTC is overexpressed in patient-derived lung adenocarcinoma samples•BTC is necessary for EGFR-mutant lung adenocarcinoma tumor growth•Loss of BTC attenuates EGFR signaling and induces apoptosisCell biology; Cancer; Transcriptomics
