NKX2-1 and neoplasm: In summary, KPU tumors exhibit similar molecular characteristics to human LUSC and display strong tumor plasticity and lineage reprogramming activity, which seems to be associated with the upregulation of squamous lineage markers (SOX2), downregulation of NKX2-1 and FOXA2, and activation of pluripotency factors such as MYC, NANOG, and KLF4.