Investigation of the molecular pathways involved in intestinal epithelial differentiation

Sade Memişoğlu, Aslı
The molecular mechanisms of balanced and continuous generation of intestinal epithelial cells, is poorly understood 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 result in an ER stress response, which is also implicated in the differentiation process. In addition, ER stress and autophagy pathways may function together under certain circumstances. The transcription factor C/EBPβ is of particular importance, as it is implicated in differentiation, ER stress and autophagy. In the current study, using two models of colorectal cancer cell lines, HT-29 and Caco-2 that can undergo differentiation, ER stress response was shown to be activated during the process of differentiation. Ca2+ flux into the cytoplasm was found to be the mediator of ER stress response in Caco-2 cells. Interestingly, ER stress caused induction of autophagy during differentiation in both cell lines.Moreover, C/EBPβ-3, the short isoform of C/EBPβ, was found to be one of the key players in the activation of autophagy. ER stress induced autophagy and involvement of C/EBPβ-3 in these processes was for the first time evidenced in the differentiation of Caco-2 and HT-29 cell lines. These results suggest new regulatory mechanisms that may be of significance in the process of intestinal epithelial differentiation.


Regulation and role of CCAAT/enhancer binding protein during differentiation of intestinal epithelial cells
Memişoğlu, Aslı Sade; Banerjee, Sreeparna (2013-09-01)
Background: The molecular mechanisms of differentiation of intestinal epithelial cells, is poorly understood and disruption of this balance may result in neoplastic transformation and malignant growth. The family of CCAAT/Enhancer Binding Protein (C/EBP) transcription factors is implicated in cellular growth, differentiation, inflammation and development and control differentiation in several cell types. The involvement of these transcription factors in intestinal differentiation is not known. The aim of th...
Investigation of the therapeutic effect of sodium butyrate in Caco-2 colon cancer cell line by using ATR-FTIR spectroscopy
Çelik, Buket; Bek, Alpan; Özek, Nihal Şimşek; Department of Micro and Nanotechnology (2018)
Sodium butyrate (NaBt), as one of the HDACi, has been demonstrated that it induces apoptosis, cell cycle arrest, the inhibition of angiogenesis, metastasis and gene expression changes. To date, there are several studies perfomed to investigate its therapeutic effect; however, theexact mechanism at molecular level is not clear yet. Therefore, the current thesis was aimed to clarify the action/theurapeutic potential mechanisms of sodium butyrate in Caco2 colon cancer cell line at molecular level using ATR-FTI...
Evaluation of methylation profiles of an epidermal growth factor receptor gene in a head and neck squamous cell carcinoma patient group
Mutlu, M.; Mutlu, Pelin; Azarkan, S.; Baylr, Ö.; Öcal, B.; Saylam, G.; KORKMAZ, MEHMET HAKAN (2021-03-23)
Upregulation of the epidermal growth factor receptor (EGFR) gene has shown an important impact on the development of head and neck cancers due to its important regulation role on multiple cell signaling pathways. The aim of this study was to investigate the methylation pattern of the promoter region of the EGFR gene between head and neck squamous cell carcinoma (HNSCC) patients and a control group. Forty-seven unrelated HNSCC patients, clinically diagnosed at the Department of Otorhinolaryngology, Dlşkapl Y...
Investigation of the inflammatory pathways in spontaneously differentiating Caco-2 cells
Astarcı, Erhan; Banerjee, Sreeparna; Çoruh, Nursen; Department of Biochemistry (2011)
Intestinal epithelial differentiation entails the formation of highly specialized cells with specific absorptive, secretory, digestive and immune functions. Cell-cell and cell-microenvironment interactions appear to be crucial in determining the outcome of the differentiation process. Using the Caco-2 cell line that can undergo spontaneous differentiation when grown past confluency, we observed a loss of VCAM1 (vascular cell adhesion molecule-1) expression while ICAM1 (intercellular cell adhesion molecule-1...
Characterization and promoter identification of metastasis associated protein 1 in human colorectal carcinoma cell lines
Tunçay Çağatay, Seda; Erson Bensan, Ayşe Elif; Department of Biology (2014)
Metastasis associated protein 1 (MTA1) is a member of the nuclear remodeling and histone deacetylase (NuRD) complex, which is known to repress the expression of several tumor suppressor genes and has been widely linked to tumor metastasis. 15-lipoxygenase-1 (15-LOX-1) is a lipid metabolizing enzyme that has tumor suppressive properties and is silenced by the NuRD complex in colorectal cancer (CRC). We have previously shown that reexpression of 15-LOX-1 inhibited metastasis in CRC, inhibited the inflammatory...
Citation Formats
A. Sade Memişoğlu, “Investigation of the molecular pathways involved in intestinal epithelial differentiation,” Ph.D. - Doctoral Program, Middle East Technical University, 2014.