Fig. 7

Enhanced USP13 expression switches lineage factor expression in KP-transformed club cells. A Experiment design: KP or KPU mice received a single intratracheal injection of cell-type-restricted Ad5-CC10-Cre virus. The experiment was terminated 11-12 weeks post-viral infection. B Representative hematoxylin and eosin (H&E) staining of KP and KPU lung at 12 weeks post-Ad5-CC10-Cre infection. Dotted line indicates a tumor nodule. Scale bar = 5 mm. C Quantification of individual tumor number (left) and area (right) in KP and KPU mice at 11-12 weeks post-virus infection (n=5 mice/group). D Representative images for H&E, USP13, NKX2-1, SPC, SOX2, and CK5 IHC stains of the KP and KPU tumors post-Ad5-CC10-Cre infection. Scale bar = 50 µm. E Quantification of NKX2-1 (left) and SOX2 (right) levels in KP and KPU tumors. F Expression of NKX2-1 and SOX2 during cancer progression in KP and KPU mice following Ad5-CC10-Cre infection. Hyperplasia (arrow) and carcinoma in situ (CIS) (dotted line) are indicated. Scale bar = 50 µm. G IHC quantification for NKX2-1 (top) and SOX2 (bottom). Each dot represents one tumor nodule. a.u., arbitrary unit. H SPC and CC10 expression during cancer progression in Ad5-CC10-Cre infected KP and KPU lungs. Hyperplasia (arrow) and carcinoma in situ (CIS) (dotted line) are indicated. Scale bar = 50 µm. (I) Schematic summarizing the expressional change of lineage factors and markers in KP and KPU club cells (CC10⁺) during lung cancer development. In (C), (E), (G), error bars indicate mean ± SEM. Two-tailed unpaired t-tests, ns = not significant, **p < 0.01, ***p < 0.001, ****p < 0.0001