SMAD4 and neoplasm: Notably, the Kruppel-like factor 5 (KLF5) had already emerged as a synthetic lethal partner for the tumor suppressor SMAD4 (31, 32) and the strong correlation between RAB10 essentiality and SMAD4 CNA observed in Depmap was similar to the one observed for KLF5 essentiality and SMAD4 CNA (Supplementary Fig. S4B).