biostudies-literatureUnknownKoo JNCI NIH HHSThe acquisition of invasive properties is a prerequisite for tumor progression and metastasis. Molecular subtypes of KRAS-driven lung cancer exhibit distinct modes of invasion that likely contribute to unique growth properties and therapeutic susceptibilities. Despite this, pre-clinical discovery strategies designed to exploit invasive phenotypes are lacking. To address this, we designed an experimental system to screen for targetable signaling pathways linked to active early invasion phenotypes in the two most prominent molecular subtypes, TP53 and LKB1, of KRAS-driven lung adenocarcinoma (LUAD). By combining live-cell imaging of human bronchial epithelial cells in a 3D invasion matrix with RNA transcriptome profiling, we identified the LKB1-specific upregulation of bone morphogenetic probioRxiv : the preprint server for biology2023.06.14.544941https://www.ebi.ac.uk/biostudies/studies/S-EPMC10312689biostudies-literatureLive-cell invasive phenotyping uncovers the ALK2/BMP6 iron homeostasis pathway as a therapeutic vulnerability in LKB1-mutant lung cancer.PMC10312689R01 CA201340P01 CA257906R01 CA194027P30 CA138292P50 CA217691R01 CA250422R01 CA236369Koo JSeong CSMarcus AIDinasarapu ARParker REZhou WDwivedi BClaussen HJohnston HRRamalingam SSTucker-Burden CFu HGilbert-Ross MArthur RAfalseLive-cell invasive phenotyping uncovers the ALK2/BMP6 iron homeostasis pathway as a therapeutic vulnerability in LKB1-mutant lung cancer.The acquisition of invasive properties is a prerequisite for tumor progression and metastasis. Molecular subtypes of KRAS-driven lung cancer exhibit distinct modes of invasion that likely contribute to unique growth properties and therapeutic susceptibilities. Despite this, pre-clinical discovery strategies designed to exploit invasive phenotypes are lacking. To address this, we designed an experimental system to screen for targetable signaling pathways linked to active early invasion phenotypes in the two most prominent molecular subtypes, TP53 and LKB1, of KRAS-driven lung adenocarcinoma (LUAD). By combining live-cell imaging of human bronchial epithelial cells in a 3D invasion matrix with RNA transcriptome profiling, we identified the LKB1-specific upregulation of bone morphogenetic pro2023-01-01T00:00:00Z2023 Jun2026-07-12T03:24:13.92Z2026-07-12T03:12:02.944ZS-EPMC103126893739824410.1101/2023.06.14.544941