PTEN Deficiency in Intestinal Epithelial Cells Inhibits Autophagy by Suppressing YKT6 Expression

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Abstract

Phosphatase and tensin homolog (PTEN) has long been considered to be a tumor-suppressing gene. Therefore, when PTEN is inhibited, it causes tumorigenesis. However, emerging evidence suggests that PTEN deficiency alone does not cause tumorigenesis in the intestine. Thus, the crucial role of PTEN in the intestine remains elusive. Autophagy is a pathway of cellular waste clearance in the intestine by degrading intracellular waste, such as misfolded proteins. Therefore, autophagy is thought of as a survival mechanism and plays a key role in preventing countless diseases; autophagy inhibition ultimately results in cell death. As preliminary data, it was found that a loss of the PTEN gene suppressed the expression of YKT6 in the intestinal epithelial cells (DLD-1). YKT6 is an R-soluble NSF attachment receptor (SNARE) protein that mediates the fusion between autophagosomes and lysosomes. While various mechanisms take place as a function of autophagy, proper lysosome function is crucial to regulate the process. Because autophagosome-lysosome fusion is required for matured autophagy, impaired YKT6 expression inhibits autophagy. Therefore, it is hypothesized that PTEN deficiency inhibits autophagy maturation through YKT6 suppression, leading to cell death. To test this hypothesis, the expression of YKT6 was examined in both control and PTEN-knockdown (KD) intestinal epithelial cells. By elucidating the role of YKT6, we hope to further the understanding of chronic inflammatory bowel diseases (IBD) and colorectal cancer.

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PTEN, YKT6, autophagy, colorectal cancer, inflammatory bowel disease

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