Autophagy is active in normal colon mucosa

Abstract

Recently, autophagy has been found to be strongly activated in colon cancer cells, but few studies have addressed the normal colon mucosa. The aim of this study was to characterize autophagy in normal human intestinal cells. We used the expression of LC3-II and BECN1 as well as SQSTM1 as markers of autophagy activity. Using the normal human intestinal epithelial crypt (HIEC) cell experimental model, we found that autophagy was much more active in undifferentiated cells than in differentiated cells. In the normal adult colonic mucosa, BECN1 was found in the proliferative epithelial cells of the lower part of the gland while SQSTM1 was predominantly found in the differentiated cells of the upper part of the gland and surface epithelium. Interestingly, the weak punctate pattern of SQSTM1 expression in the lower gland colocalized with BECN1-labeled autophagosomes. The usefulness of SQSTM1 as an active autophagy marker was confirmed in colon cancer specimens at the protein and transcript levels. In conclusion, our results show that autophagy is active in the colonic gland and is associated with the intestinal proliferative/undifferentiated and progenitor cell populations.

RNF216 contributes to proliferation and migration of colorectal cancer via suppressing BECN1-dependent autophagy

“…A recent study showed that both BECN1 over- and under-expression could be related to poor colon cancer prognosis, illustrating the multifunctionality of BECN1 and autophagy in cancer aggressiveness [34, 35]. Our results confirmed the inhibitory role of autophagy in CRC development, consistent with other reports of BECN1-mediated tumor progression inhibition.…”

Alteration of p62/SQSTM1 Expression Is Uncommon in Gastrointestinal and Prostate Cancer Tissues

“…p62 is highly expressed in breast, lung, gastric, colon, esophageal, and hepatocellular carcinomas and is associated with poor cancer patient prognosis 3-6. In contrast, a recent study reported that p62 was downregulated in colon carcinomas 7. The aim of our study was to confirm whether p62 expression is altered in gastric and colorectal cancers and to address whether it is altered in other cancers.…”

Autophagy Enhances Intestinal Epithelial Tight Junction Barrier Function by Targeting Claudin-2 Protein Degradation

“…Autophagy refers to the engulfment and processing of cellular proteins, including damaged organelles and long-lived and misfolded proteins. Autophagy has been shown to be active in the normal colonic intestinal mucosa, more so in the proliferative component of colonic crypts (7), and has been suggested to play a role in intestinal cell survival during physiological stress (8). Among intestinal diseases, autophagy was first linked to pathogenesis of Crohn disease when genome-wide association studies identified mutations in the autophagy-related genes ATG16L1 and IRGM as risk factors for Crohn disease (9 -11).…”