Dataset Information

Slit2/Robo1 signaling promotes intestinal tumorigenesis through Src-mediated activation of the Wnt/?-catenin pathway.

ABSTRACT: Slit2 is often overexpressed in cancers. Slit2 is a secreted protein that binds to Roundabout (Robo) receptors to regulate cell growth and migration. Here, we employed several complementary mouse models of intestinal cancers, including the Slit2 transgenic mice, the ApcMin/+ spontaneous intestinal adenoma mouse model, and the DMH/DSS-induced colorectal carcinoma model to clarify function of Slit2/Robo1 signaling in intestinal tumorigenesis. We showed that Slit2 and Robo1 are overexpressed in intestinal tumors and may contribute to tumor generation. The Slit2/Robo1 signaling can induce precancerous lesions of the intestine and tumor progression. Ectopic expression of Slit2 activated Slit2/Robo1 signaling and promoted tumorigenesis and tumor growth. This was mediated in part through activation of the Src signaling, which then down-regulated E-cadherin, thereby activating Wnt/?-catenin signaling. Thus, Slit2/Robo1 signaling is oncogenic in intestinal tumorigenesis.

SUBMITTER: Zhang QQ

PROVIDER: S-EPMC4413642 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Slit2/Robo1 signaling promotes intestinal tumorigenesis through Src-mediated activation of the Wnt/β-catenin pathway.

Zhang Qian-Qian QQ Zhou Da-Lei DL Lei Yan Y Zheng Li L Chen Sheng-Xia SX Gou Hong-Ju HJ Gu Qu-Liang QL He Xiao-Dong XD Lan Tian T Qi Cui-Ling CL Li Jiang-Chao JC Ding Yan-Qing YQ Qiao Liang L Wang Li-Jing LJ

Oncotarget 20150201 5

Slit2 is often overexpressed in cancers. Slit2 is a secreted protein that binds to Roundabout (Robo) receptors to regulate cell growth and migration. Here, we employed several complementary mouse models of intestinal cancers, including the Slit2 transgenic mice, the ApcMin/+ spontaneous intestinal adenoma mouse model, and the DMH/DSS-induced colorectal carcinoma model to clarify function of Slit2/Robo1 signaling in intestinal tumorigenesis. We showed that Slit2 and Robo1 are overexpressed in int ...[more]

PMID: 25605242

Similar Datasets

Project description:AimsPrevious reports indicated that the Slit2-Robo signalling pathway is involved in embryonic heart development and fibrosis in other solid organs, but its function in adult cardiac fibrosis has not been investigated. Here, we investigate the role of the Slit2-Robo1 signalling pathway in cardiac fibrosis.Methods and resultsThe right atrial tissue samples were obtained from patients with valvular heart disease complicated by atrial fibrillation during heart valve surgery and from healthy heart donors. The fibrotic animal model is created by performing transverse aortic constriction (TAC) surgery. The Robo1, Slit2, TGF-?1, and collagen I expression levels in human and animal samples were evaluated by immunohistochemistry and western blot analysis. Echocardiography measured the changes in heart size and cardiac functions of animals. Angiotensin II (Ang II), Slit2-siRNA, TGF-?1-siRNA, recombinant Slit2, and recombinant TGF-?1 were transfected to cardiac fibroblasts (CFs) respectively to observe their effects on collagen I expression level. The right atrial appendage of patients with valvular heart disease complicated by atrial fibrillation found significantly up-regulated Slit2, Robo1, TGF-?1, and collagen I expression levels. TAC surgery leads to heart enlargement, cardiac fibrosis, and up-regulation of Slit2, Robo1, TGF-?1, and collagen I expression levels in animal model. Robo1 antagonist R5 and TGF-?1 antagonist SB431542 suppressed cardiac fibrosis in TAC mice. Treatment with 100 nM Ang II in CFs caused significantly increased Slit2, Robo1, Smad2/3, TGF-?1, collagen I, PI3K, and Akt expression levels. Transfecting Slit2-siRNA and TGF-?1-siRNA, respectively, into rat CFs significantly down-regulated Smad2/3 and collagen I expression, inhibiting the effects of Ang II. Recombinant Slit2 activated the TGF-?1/Smad signalling pathway in CFs and up-regulated Periostin, Robo1, and collagen I expression.ConclusionsThe Slit2-Robo1 signalling pathway interfered with the TGF-?1/Smad pathway and promoted cardiac fibrosis. Blockade of Slit2-Robo1 might be a new treatment for cardiac fibrosis.

Dataset Information

Slit2/Robo1 signaling promotes intestinal tumorigenesis through Src-mediated activation of the Wnt/?-catenin pathway.

Publications

Slit2/Robo1 signaling promotes intestinal tumorigenesis through Src-mediated activation of the Wnt/β-catenin pathway.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets