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Human lung adenocarcinoma exhibits a propensity for de-differentiation, complicating diagnosis and treatment, and predicting poorer patient survival. In genetically engineered mouse models of lung cancer, expression of the BRAF V600E oncoprotein kinase initiates the growth of benign tumors retaining characteristics of their cell of origin, AT2 pneumocytes. Cooperating alterations that activate PI3'-lipid signaling promote progression of BRAF V600E -driven benign tumors to malignant adenocarcinoma. However, the mechanism(s) by which this cooperation occurs remains unclear. To address this, we generated mice carrying a conditional Braf CAT allele in which CRE-mediated recombination leads to co-expression of BRAF V600E and tdTomato. We demonstrate that co-expression of BRAF V600E and PIK3CA H1047R in AT2 pneumocytes leads to rapid cell de-differentiation, without decreased expression of the transcription factors NKX2-1, FOXA1, or FOXA2. Instead, we propose a novel role for PGC1α in maintaining AT2 pneumocyte identity. These findings provide insight into how these pathways may cooperate in the pathogenesis of human lung adenocarcinoma., Competing Interests: Jv, MS, JB, MC, AL, AL, SG, CT No competing interests declared, MM Reviewing editor, eLife, (© 2019, van Veen et al.)