LKB1 drives stasis and C/EBP-mediated reprogramming to an alveolar type II fate in lung cancer

• DOI: 10.1038/s41467-022-28619-8
• Publication Date: 2022-02-28T11:03:34Z
• Authors: Christopher W. Mu...; Jennifer J. Brady; Mingqi Han; Hongchen Cai; Min K. Tsai; Sarah E. Pierce; Ran Cheng; Janos Demeter; David M. Feldser; Peter K. Jackson; David B. Shackelford; Monte M. Winslow
• Keywords: Reprogramming

Abstract LKB1 is among the most frequently altered tumor suppressors in lung adenocarcinoma. Inactivation of Lkb1 accelerates growth and progression oncogenic KRAS-driven tumors mouse models. However, molecular mechanisms by which constrains tumorigenesis whether cancer state that stems from deficiency can be reverted remains unknown. To identify processes governed vivo, we generated an allele enables inactivation at initiation subsequent restoration established tumors. Restoration suppressed proliferation led to stasis. activated targets C/EBP transcription factors drove neoplastic cells a progenitor-like less proliferative alveolar type II cell-like state. We show govern subset genes are induced depend upon NKX2-1. also demonstrate defining factor lineage, C/EBPα, vivo. Thus, this key suppressor regulates lineage-specific factors, thereby constraining development through enforced differentiation.