STAT3 and SMAD4 play opposing roles in pancreatic tumorigenesis
A. Representative H&E staining of pancreatic tumor sections derived from KPC cells of the indicated genotypes, SMAD4 KO (n=12), SMAD4/STAT3 DKO (n=3) and TGFBR2/STAT3 DKO (n=3). At least two independent clones were used. Scale bar = 100μm
B. Western blot analysis of control (Intact), STAT3 KO (ST3KO), STAT3/SMAD4 double KO (ST3/SM4DKO), or STAT3/TGFBR2 double KO (ST3/TRB2DKO) KPC cells. Expression of STAT3, SMAD4, TGFBR2, CDH1 (E-cadherin), and VIM (Vimentin) is shown. ERK1/2 is a loading control.
C. Summary of pancreatic tumor development in nude mice by KPC cells of the indicated STAT3, SMAD4, and TGFBR2 genotypes presented.
D. Pearson correlation heatmap comparing gene expression of SMAD4 KO (SMAD4KO_up, down) and STAT3 KO (STAT3KO_up, down) KPC cells with human PDACs from TCGA (n=168). Signature scores were calculated using the top up- and down-regulated genes in STAT3 and SMAD4 KO KPC cells. The number of genes for each comparison is shown.
E. Pearson correlation heatmap comparing gene expression signature scores of genes regulated in STAT3 KO KPC cells with pancreatic tumors from the COMPASS database (n=92) classified by RAS dependency index (RDI), KRAS-dependent signature (KRAS-sig), KRAS-independent signature (RSK-sig), epithelial (EPI) or mesenchymal (MES) gene signature score.