Differentiation of Caco-2 cells requires both transcriptional and post-translational down-regulation of Myc

Caco-2 cancer cell line is widely used to reproduce in vitro the differentiation of absorptive enterocytes of human intestinal epithelium. This cell line, when cultured over confluence for 21 days, spontaneously undergoes cell cycle arrest and differentiates with the formation of a polarized enterocyte-like monolayer. During this process, Myc protein is completely down-regulated, as occurs in normal enterocytes. Caco-2 cells differ from normal enterocytes for mutations of APC and β-catenin genes, factors known to be involved in the transcriptional control of MYC gene during enterocyte differentiation. In this paper, we investigated how Myc regulation could be achieved during Caco-2 differentiative process, notwithstanding the APC and β-catenin mutations. We highlighted the post translational regulation of Myc protein as one of the essential mechanisms that allows the exit from cell cycle and onset of differentiation of Caco-2 cells. Moreover, we found a strong correlation between Myc protein downregulation and the expression of the transcription factor Cdx2, suggesting the existence of a regulative link between these two proteins.