南京医科大学:沙门氏菌感染影响Wnt1表达并影响结直肠癌进展
创作:女巫 审核:aluba 2018年09月22日
  • 在体内和体外实验中,沙门氏菌的定殖显著降低了肠上皮细胞中的Wnt1表达水平;
  • 沙门氏菌通过表达AvrA下调Wnt1的表达水平,在慢性沙门氏菌感染的癌症模型中,AvrA+沙门氏菌感染组的Wnt1蛋白水平降低;
  • Wnt1的表达下调在沙门氏菌感染中对细胞起保护作用,并抑制沙门氏菌感染引起的肠道炎症;
  • 通过Crispr-Cas9下调Wnt1表达,抑制了癌细胞的侵袭和迁移;
  • Wnt1在人类结直肠癌(CRC)组织中下调,提示Wnt1与癌症进展相关。
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来自南京医科大学团队在Neoplasia上发表的一项最新研究,发现沙门氏菌可通过表达一种效应蛋白——AvrA,下调Wnt1的表达,Wnt1的下调在肠道炎症中起保护作用,并抑制沙门氏菌侵染细胞。另外,下调Wnt1还能够抑制肿瘤细胞的侵袭和迁移,而结直肠癌患者肿瘤组织中的Wnt1表达下调,提示细菌感染引起的Wnt1表达改变在结直肠癌进展中的作用。
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Neoplasia [IF:6.218]

Novel Regulatory Roles of Wnt1 in Infection-Associated Colorectal Cancer

Wnt1在感染相关结直肠癌中的新型调节作用

10.1016/j.neo.2018.03.001

2018-04-05, Article

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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.

First Authors:
Jianwei Wang,Rong Lu

Correspondence Authors:
Xingyin Liu,Jun Sun

All Authors:
Jianwei Wang,Rong Lu,Xinhui Fu,Zhou Dan,Yong-Guo Zhang,Xinxia Chang,Qisha Liu,Yinglin Xia,Xingyin Liu,Jun Sun

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