Novel Regulatory Roles of Wnt1 in Infection-Associated Colorectal Cancer.
Novel Regulatory Roles of Wnt1 in Infection-Associated Colorectal Cancer.
复制标题
Wnt1 在感染相关结直肠癌中的新调节作用
DOI：
10.1016/j.neo.2018.03.001
复制
发表时间：
2018-05
期刊：
影响因子：
--
通讯作者：
Sun J
中科院分区：
文献类型：
--
作者：
Wang J;Lu R;Fu X;Dan Z;Zhang YG;Chang X;Liu Q;Xia Y;Liu X;Sun J
沙门氏菌感染是一个主要的公共卫生问题，在人类中的定居可能是慢性的，并增加了患癌症的风险。WNT信号是肠道更新和发育、炎症和肿瘤发生的关键途径。在目前的研究中，我们使用细胞培养模型、沙门氏菌结肠炎结肠癌模型和人类样本报告了WNT1在感染和结肠癌中的新作用。与细菌诱导的WNT2和WNT11的增加相反，沙门氏菌在体内和体外的定植显著降低了肠上皮细胞中WNT1的水平。已知细菌AvrA蛋白激活典型的Wnt途径。在沙门氏菌结肠炎小鼠的肠道中，表达AvrA的沙门氏菌下调了WNT1的表达水平，但稳定了表达AvrA的沙门氏菌的表达。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方法下调WNT1促进了癌细胞的侵袭和迁移。有趣的是，我们发现Wnt1在人类结直肠癌组织中表达下调，并且Wnt1表达下调可能与肿瘤进展相关。我们的研究为肠道细菌调节WNT1表达并可能导致感染相关结肠癌的机制提供了见解。
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 promoted 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.
登录
查看更多内容
肠道菌群，炎症和结直肠癌。
影响因子：
6.8
作者：
Sun J;Kato I
通讯作者：
Kato I
影响因子：
--
作者：
Lu R;Bosland M;Xia Y;Zhang YG;Kato I;Sun J
通讯作者：
Sun J
影响因子：
4.6
作者：
Martz SL;McDonald JA;Sun J;Zhang YG;Gloor GB;Noordhof C;He SM;Gerbaba TK;Blennerhassett M;Hurlbut DJ;Allen-Vercoe E;Claud EC;Petrof EO
通讯作者：
Petrof EO
影响因子：
3.8
作者：
Kenny PA;Enver T;Ashworth A
通讯作者：
Ashworth A
影响因子：
29.4
作者：
Gradel, Kim O.;Nielsen, Hans L.;Nielsen, Henrik
通讯作者：
Nielsen, Henrik