Nanog maintains stemness of Lkb1-deficient lung adenocarcinoma and prevents gastric differentiation.

ABSTRACT: Growing evidence supports that LKB1-deficient KRAS-driven lung tumors represent a unique therapeutic challenge, displaying strong cancer plasticity that promotes lineage conversion and drug resistance. Here we find that murine lung tumors from the Kras^LSL-G12D/+ ; Lkb1^flox/flox (KL) model show strong plasticity, which associates with up-regulation of stem cell pluripotency genes such as Nanog. Deletion of Nanog in KL model initiates a gastric differentiation program and promotes mucinous lung tumor growth. We find that NANOG is not expressed at a meaningful level in human lung adenocarcinoma (ADC), as well as in human lung invasive mucinous adenocarcinoma (IMA). Gastric differentiation involves activation of Notch signaling, and perturbation of Notch pathway by the γ-

SUBMITTER: Tong X 

PROVIDER: S-EPMC7933951 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature