Development of lung adenocarcinoma is often associated with dysregulation of lung epithelial lineage-determining transcriptional regulators that govern differentiation status.47 For example, Gata6 maintains proper alveolar maturation18 in cooperation with other known lineage-specific transcription factors such as Hopx19 and Nkx2-1.20Runx3 is required for both bronchiolar and alveolar lineage differentiation.48, 49 Among the differentiation regulators, the roles of Nkx2-1 and Runx3 in oncogenic K-Ras-induced lung tumorigenesis have been most extensively studied. This evidence concerns the gene KRAS and lung adenocarcinoma.