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Fig. 2 | Molecular Cancer

Fig. 2

From: Stem cells in homeostasis and cancer of the gut

Fig. 2

Intestinal cell plasticity dynamics in malignant transformation. (a) ISCs have the ability to effectively initiate adenoma formation when these cells acquire Apc mutations. On the other hand, differentiated intestinal epithelial cells do rarely undergo malignant transformation upon obtaining an oncogenic hit. (b) However, in an inflammatory environment differentiated cells acquire similar transformation potential. Different factors underlie the differences in transformation capacity of ISCs versus differentiated cells. First of all, the topological position of differentiated cells prevents them in homeostasis from generating long-lived clonal lineages. Secondly, the ISC niche endows ISCs with the potential to endure the stressors that result from acquiring an oncogenic mutation [74]. Similarly, in a colitis environment the differentiated cell compartment is also installed with anti-apoptotic capacities through activation of the nuclear factor-κB (Nf-κB) pathway [73]. The anti-apoptotic protein BLC-2 is one of the identified mediators that facilitates this oncogenic transformation. Indeed, inhibition of BCL-2, either genetically or pharmacologically, reduced adenoma burden in mice [74]

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