SMAD4 and cancer: However, KRAS/SMAD4 KO KPC cells displayed sharply reduced expression of EMT-related genes (e.g., Acta2, Col3a1, and Vim), while RAS signature genes defined for the ability to sustain epithelial differentiation and viability of KRAS mutant cancer cells (e.g., Cdh1, Itgb6, and Prom1)13 were among the most upregulated (Fig. 1h).