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Novel Regulatory Roles of Wnt1 in Infection-Associated Colorectal Cancer.
Neoplasia ( IF 6.3 ) Pub Date : 2018-04-08 , DOI: 10.1016/j.neo.2018.03.001
Jianwei Wang 1 , Rong Lu 2 , Xinhui Fu 3 , Zhou Dan 4 , Yong-Guo Zhang 2 , Xinxia Chang 4 , Qisha Liu 4 , Yinglin Xia 2 , Xingyin Liu 1 , Jun Sun 5
Affiliation  

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.

中文翻译:

Wnt1在感染相关的大肠癌中的新型调控作用。

沙门氏菌感染是主要的公共卫生问题,人类的定殖可能是长期的,并增加了患癌症的风险。Wnt信号传导是肠道更新与发育,炎症和肿瘤发生的关键途径。在当前的研究中,我们报告了Wnt1在感染和结肠癌中的新作用,使用细胞培养模型,沙门氏菌-结肠炎结肠癌模型和人类样品。与细菌诱导的Wnt2和Wnt11的增加相反,沙门氏菌定植显着降低了体内和体外肠上皮细胞中Wnt1的水平。已知细菌AvrA蛋白可激活经典的Wnt途径。在沙门氏菌-结肠炎小鼠肠道中,表达AvrA的沙门氏菌下调了Wnt1的表达水平,但通过AvrA缺失的沙门氏菌使Wnt1的表达水平稳定。在慢性沙门氏菌感染的癌症模型中,AvrA +感染组的Wnt1蛋白水平降低。因此,我们进一步评估了Wnt1下调在炎症反应和结直肠癌(CRC)进展中的功能作用。此外,通过Crispr-Cas9方法对Wnt1的下调影响了癌细胞的侵袭和迁移。有趣的是,我们发现Wnt1在人类CRC组织中下调,而Wnt1下调可能与癌症进展相关。我们的研究为肠道细菌调节Wnt1表达并可能导致感染相关的结肠癌的机制提供了见识。我们进一步评估了Wnt1下调在炎症反应和结直肠癌(CRC)进展中的功能作用。此外,通过Crispr-Cas9方法对Wnt1的下调影响了癌细胞的侵袭和迁移。有趣的是,我们发现Wnt1在人类CRC组织中下调,而Wnt1下调可能与癌症进展相关。我们的研究提供了肠道细菌调节Wnt1表达并可能导致感染相关结肠癌的机制的见解。我们进一步评估了Wnt1下调在炎症反应和结直肠癌(CRC)进展中的功能作用。此外,通过Crispr-Cas9方法对Wnt1的下调影响了癌细胞的侵袭和迁移。有趣的是,我们发现Wnt1在人类CRC组织中下调,而Wnt1下调可能与癌症进展相关。我们的研究为肠道细菌调节Wnt1表达并可能导致感染相关的结肠癌的机制提供了见识。
更新日期:2019-11-01
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