“…While intestinal stem cells are not the only cell capable of serving as the cell of origin (Visvader, 2011), they are by far the most efficient, requiring only a single activating mutation of the WNT/β-catenin pathway - a frequent event associated with the progression of the majority of CRCs, such as APC mutations in adenocarcinomas (Clevers and Nusse, 2012; Sekine et al, 2016). Paradoxically, despite a high prevalence among colorectal tumors, ectopic expression of an oncogenic BRAF mutant transgene promotes either senescence or differentiation of intestinal stem cells (Carragher et al, 2010; Riemer et al, 2015). Thus, while oncogenic activation of BRAF can eventually lead to tumor formation in mouse models, these tumors are slow to arise (Rad et al, 2013; Sakamoto et al, 2017).…”