KLF4 promotes a KRT13+ hillock-like state in squamous lung cancer.

ABSTRACT: Lung squamous cell carcinoma (LUSC) is basal-like subtype of lung cancer with limited treatment options. While prior studies have identified tumor-propagating cell states in squamous tumors, the broader landscape of intra-tumoral heterogeneity within LUSC remains poorly understood. Here, we employ Sox2-driven mouse models, organoid cultures, and single-cell transcriptomic analyses to uncover previously unrecognized levels of cell fate diversity within LUSC. Specifically, we identify a KRT13⁺ hillock-like population of slower-dividing tumor cells characterized by immunomodulatory gene expression signatures. The tumor hillock-like state is conserved across multiple animal models and is present in the majority of human LUSCs as well as head and neck and esophageal squamous tumors.

SUBMITTER: Izzo LT 

PROVIDER: S-EPMC11952405 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature