Novel Regulatory Roles of Wnt1 in Infection-Associated Colorectal Cancer.

Abstract

Salmonella infection is a major public health concern, and colonization in humans can be chronic and increases the risk of cancers. Wnt signaling is a key pathway for intestinal renewal and development, inflammation, and tumorigenesis. In the current study, we report a novel role of Wnt1 in infection and colon cancer using cell culture models, a Salmonella-colitis colon cancer model, and human samples. In contrast to the bacteria-induced increases in Wnt2 and Wnt11, Salmonella colonization significantly reduced the level of Wnt1 in intestinal epithelial cells in vivo and in vitro. The bacterial AvrA protein is known to activate the canonical Wnt pathway. Wnt1 expression level was downregulated by AvrA-expressing Salmonella but stabilized by AvrA-deficient Salmonella in the intestine of Salmonella-colitis mice. In a chronic Salmonella-infected cancer model, the Wnt1 protein level was decreased in the AvrA+ infected group. Thus, we further assessed the functional role of Wnt1 downregulation in the inflammatory response and colorectal cancer (CRC) progression. Moreover, downregulation of Wnt1 by the Crispr-Cas9 method affected cancer cell invasion and migration. Interestingly, we found that Wnt1 was downregulated in human CRC tissue, and Wnt1 downregulation may be correlated with cancer progression. Our study provides insights into mechanisms by which enteric bacteria regulate Wnt1 expression and potentially contribute to infection-associated colon cancer.

• Authors: Jianwei Wang, Rong Lu, Xinhui Fu, Zhou Dan, Yong-Guo Zhang, Xinxia Chang, Qisha Liu, Yinglin Xia, Xingyin Liu, Jun Sun
• Journal: Neoplasia (New York, N.Y.) (Neoplasia) Vol. 20 Issue 5 Pg. 499-509 (05 2018) ISSN: 1476-5586 [Electronic] United States
• PMID: 29626750 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 UIC. Published by Elsevier Inc. All rights reserved.

Chemical References

• Bacterial Proteins
• WNT1 protein, human
• Wnt1 Protein

Topics

• Animals
• Bacterial Proteins (metabolism)
• Caco-2 Cells
• Colon (metabolism, microbiology)
• Colorectal Neoplasms (etiology, metabolism, microbiology)
• Epithelial Cells (metabolism, microbiology)
• Female
• HCT116 Cells
• Humans
• Inflammation (metabolism, microbiology)
• Intestinal Mucosa (metabolism, microbiology)
• Mice
• Mice, Inbred C57BL
• Salmonella (metabolism)
• Salmonella Infections (complications)
• Wnt Signaling Pathway (physiology)
• Wnt1 Protein (metabolism)