KLF4 promotes a KRT13+ hillock-like state in squamous lung cancer DOI Creative Commons
Luke Izzo,

Tony Reyes,

Srijan Meesala

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Март 13, 2025

Lung squamous cell carcinoma (LUSC) is basal-like subtype of lung cancer with limited treatment options. While prior studies have identified tumor-propagating states in tumors, the broader landscape 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 fate diversity LUSC. Specifically, identify a KRT13 + hillock-like population slower-dividing tumor cells characterized by immunomodulatory gene expression signatures. The state conserved across multiple animal models present majority human LUSCs as well head neck esophageal tumors. Our findings shed light on cellular origins states: normal club give rise tumors luminal populations, while transition into basal states, resembling homeostatic responses injury. Mechanistically, KLF4 key transcriptional regulator state, both necessary sufficient induce expression. Together, these results provide new molecular insights plasticity that underlies LUSC, offering potential avenues for therapeutic strategies.

Язык: Английский

KLF4 promotes a KRT13+ hillock-like state in squamous lung cancer DOI Creative Commons
Luke Izzo,

Tony Reyes,

Srijan Meesala

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Март 13, 2025

Lung squamous cell carcinoma (LUSC) is basal-like subtype of lung cancer with limited treatment options. While prior studies have identified tumor-propagating states in tumors, the broader landscape 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 fate diversity LUSC. Specifically, identify a KRT13 + hillock-like population slower-dividing tumor cells characterized by immunomodulatory gene expression signatures. The state conserved across multiple animal models present majority human LUSCs as well head neck esophageal tumors. Our findings shed light on cellular origins states: normal club give rise tumors luminal populations, while transition into basal states, resembling homeostatic responses injury. Mechanistically, KLF4 key transcriptional regulator state, both necessary sufficient induce expression. Together, these results provide new molecular insights plasticity that underlies LUSC, offering potential avenues for therapeutic strategies.

Язык: Английский

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