NKX2-1 controls lung cancer progression by inducing DUSP6 to dampen ERK activity.

The RAS→RAF→MEK→ERK pathway is hyperactivated in the majority of human lung adenocarcinoma (LUAD). However, the initial activating mutations induce homeostatic feedback mechanisms that limit ERK activity. How ERK activation reaches the tumor-promoting levels that overcome the feedback and drive malignant progression is unclear.

An NKX2-1/ERK/WNT feedback loop modulates gastric identity and response to targeted therapy in lung adenocarcinoma.

Cancer cells undergo lineage switching during natural progression and in response to therapy. NKX2-1 loss in human and murine lung adenocarcinoma leads to invasive mucinous adenocarcinoma (IMA), a lung cancer subtype that exhibits gastric differentiation and harbors a distinct spectrum of driver oncogenes. In murine BRAF-driven lung adenocarcinoma, NKX2-1 is required for early tumorigenesis, but dispensable for established tumor growth.