Abstract |
Slit2 (slit guidance ligand 2), a ligand of the Roundabout1 (Robo1) transmembrane receptor, is often overexpressed in colorectal carcinomas ( CRCs). In this study, we performed data mining in the Metabolic gEne RApid Visualizer (MERAV) database and found that Slit2 and TGF-β1 ( Transforming growth factor-β1) are highly expressed in carcinomas relative to those in tumor-free tissues from healthy volunteers or wild type mice. Furthermore, expression of Slit2 and TGF-β1 in CRCs increases with pathological stages. Serum levels of Slit2 in patients with CRC and in ApcMin/+ mice with spontaneous intestinal adenoma were significantly increased compared with those in healthy controls. Specific blockage of Slit2 binding to Robo1 inactivated TGF-β/Smads signaling and inhibited tumor cell migration and metastasis, which can be partially restored by treatment with TGF-β1. However, specific inhibition of TGF-β1/Smads signaling reduced CRC tumor cell migration and invasion without affecting cell proliferation. This study suggests that activation of Slit2/Robo1 signaling in CRC induces tumor metastasis partially through activation of the TGF-β/Smads pathway.
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Authors | Yuying Yao, Zijun Zhou, Liuyou Li, Junchen Li, Lixun Huang, Jiangchao Li, Cuiling Qi, Lingyun Zheng, Lijing Wang, Qian-Qian Zhang |
Journal | Cells
(Cells)
Vol. 8
Issue 6
(06 25 2019)
ISSN: 2073-4409 [Print] Switzerland |
PMID | 31242633
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Intercellular Signaling Peptides and Proteins
- Nerve Tissue Proteins
- Receptors, Immunologic
- Smad Proteins
- Transforming Growth Factor beta
- Slit homolog 2 protein
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Topics |
- Animals
- Cell Line, Tumor
- Cell Movement
- Cell Proliferation
- Colorectal Neoplasms
(metabolism, pathology)
- Humans
- Intercellular Signaling Peptides and Proteins
(metabolism)
- Mice
- Neoplasm Invasiveness
- Neoplasm Metastasis
- Nerve Tissue Proteins
(metabolism)
- Rats
- Receptors, Immunologic
(metabolism)
- Signal Transduction
- Smad Proteins
(metabolism)
- Transforming Growth Factor beta
(metabolism)
- Roundabout Proteins
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