Critical role for a high-plasticity cell state in lung cancer

Plasticity—the ability of cells to undergo phenotypic transitions—drives cancer progression and therapy resistance1–3. Recent studies have suggested that plasticity in solid tumours is concentrated in a minority subset of cancer cells4–6, yet functional studies examining this high-plasticity cell state (HPCS) in situ are lacking. Here we develop mouse models enabling the detection, longitudinal lineage tracing and ablation of the HPCS in autochthonous lung tumours in vivo. Lineage tracing reveals that the HPCS cells possess a high capacity for cell state transitions, giving rise to both early neoplastic (differentiated) and progressed lung cancer cell states in situ. Longitudinal lineage tracing using secreted…