Figure 3.

SMAD4 expression alters ECM and secretory pathway genes. (A) GSEA analysis shows Tgfβ signaling genes are significantly upregulated in SMAD4-expressing tumor organoids. GSEA analysis shows MYC targets are significantly downregulated in SMAD4+ organoids grown in BME. (B) Heatmap of significantly regulated (log2FC < −1 and >1, adj p-value < 0.05) pINDUCER-SMAD4 Smad4^KO BRAF^V600E/+ organoids untreated (−Dox) (n = 4) and treated (+Dox) with 4 μg/mL Doxycycline treatment (n = 2). (C) GO Terms show significant upregulation in gene sets related to extracellular region, intermediate filaments, and n-linked asparagine in tumor organoids grown in BME with expression of SMAD4 induced via doxycycline. (D) GO Terms show significant downregulation in gene sets related to positive regulation of MAPK cascade, cell-to-cell signaling, and n-linked asparagine in tumor organoids grown in BME with expression of SMAD4 induced via doxycycline.