Activation of C/EBPbeta-3 during cellular differentiation links the development of ER stress and autophagy in colon epithelial cells

2016-09-01
Memişoğlu, Aslı Sade
Tuncer, S.
Banerjee, Sreeparna
The molecular mechanisms of balanced and continuous generation of intestinal epithelial cells, is closely regulated and disruption of this balance may result in neoplastic transformation and malignant growth. Differentiation is regulated by numerous signals, which in turn regulate signaling pathways directing activation or inactivation of certain transcription factors. Perturbations like changes in Ca2+levels, glucose or amino acid starvation may result in an ER stress response, which is also implicated in the differentiation process. In addition, ER stress and autophagypathways may function together under certain circumstances.The transcription factor C/EBPbeta is implicated in differentiation, ER stress and autophagy. In the current study, we have used Caco-2 and HT-29, twocolorectal cancer cell lines that can under go spontaneous differentiation after reaching 100% confluency, or through glucosedeprivation respectively to enterocyte like cells. We haveobserved an ER stress response to be activated during the process of differentiation. Ca2+flux into the cytoplasm was foundto be the mediator of ER stress response in Caco-2 cells.Interestingly, ER stress also caused induction of autophagy during differentiation in both cell lines. Moreover, ER stress resulted in the up regulation of C/EBPbeta-3, a short isoform of C/EBPbeta generated through alternative translation, whichthen orchestrated the activation of autophagy. ChIP-seq revealed that C/EBPbeta was enriched in the promoters of genes related to metabolism, junctional and membrane proteins, endocytosis and differentiation and proliferation in intestinal epithelial cells.We have shown here for the first time that ER stress inducedautophagy and the involvement of C/EBPbeta-3 in these processes in the differentiation of Caco-2 and HT-29 cell lines. Theseresults suggest new regulatory mechanisms that may be of significance in the process of intestinal epithelial differentiation.

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Citation Formats
A. S. Memişoğlu, S. Tuncer, and S. Banerjee, “Activation of C/EBPbeta-3 during cellular differentiation links the development of ER stress and autophagy in colon epithelial cells,” 2016, vol. 283, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/53609.