Isam Khalaila
Ben Gurion University, Israel
Title: The Role of O-GlcNAcylation on Colorectal cancer EMT and tumorigenicity
Biography
Biography: Isam Khalaila
Abstract
The Wnt/β-catenin signaling pathway and cadherin-mediated adhesion are implicated in epithelial-mesenchymal transition (EMT), a key cellular process in invasion and metastasis. O-GlcNAcylation, the addition of β-N-acetylglucosamine (O-GlcNAc) moiety to Ser/Thr residues is involved in cancer and tumorigenicity. The current study is aiming to investigate the effect of O-GlcNAcylation on β-catenin and E-cadherin expression and function and thus, on EMT, cell motility and cancer cell tumorigenicity. The enzyme machinery of O-GlcNAcylation was modulated either with chemical inhibitors or by gene silencing. When O-GlcNAcase (OGA), the enzyme responsible for the removal of O-GlcNAc, inhibited or silences, a global elevation of protein O-GlcNAcylation and increase in the expression of E-cadherin and b-catenin were noted. Concomitantly with enhanced O-GlcNAcylation, b-catenin import into the nucleus and its transcriptional activity were elevated. Additionally, fibroblast cell motility was enhanced. Consistent with the results obtained by OGA inhibition, OGT-silencing led to a significant reduction in b-catenin level. Murine orthotropic colorectal cancer model indicates that elevated O-GlcNAcylation leads to increased mortality rate. However, reduction in O-GlcNAcylation promoted survival and attenuation of metastases development. The results described herein provide circumstantial clues that O-GlcNAcylation deregulates β-catenin and E-cadherin expression and activity in fibroblast cell lines and this might impact EMT and cell motility, which may further influence tumorigenicity and metastasis.