Slit-Robo signaling induces malignant transformation through Hakai-mediated E-cadherin degradation during colorectal epithelial cell carcinogenesis
文献类型：期刊论文
| 作者 | Zhou, WJ; Geng, ZH; Chi, S; Zhang, WL; Niu, XF; Lan, SJ; Ma, L; Yang, XS; Wang, LJ; Ding, YQ |
| 刊名 | CELL RESEARCH
 |
| 出版日期 | 2011 |
| 卷号 | 21期号:4页码:609-626 |
| 关键词 | colorectal carcinogenesis E-cadherin Hakai Robo Slit |
| 通讯作者 | Geng, JG (reprint author), Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA.,dyqsmu@sina.com ; genglab@gmail.com |
| 英文摘要 | The Slit family of guidance cues binds to Roundabout (Robo) receptors and modulates cell migration. We report here that ectopic expression of Slit2 and Robo1 or recombinant Slit2 treatment of Robo1-expressing colorectal epithelial carcinoma cells recruited an ubiquitin ligase Hakai for E-cadherin (E-cad) ubiquitination and lysosomal degradation, epithelial-mesenchymal transition (EMT), and tumor growth and liver metastasis, which were rescued by knockdown of Hakai. In contrast, knockdown of endogenous Robo1 or specific blockade of Slit2 binding to Robo1 prevented E-cad degradation and reversed EMT, resulting in diminished tumor growth and liver metastasis. Ectopic expression of Robo1 also triggered a malignant transformation in Slit2-positive human embryonic kidney 293 cells. Importantly, the expression of Slit2 and Robo1 was significantly associated with an increased metastatic risk and poorer overall survival in colorectal carcinoma patients. We conclude that engagement of Robo1 by Slit2 induces malignant transformation through Hakai-mediated E-cad ubiquitination and lysosomal degradation during colorectal epithelial cell carcinogenesis. |
| 学科主题 | Cell Biology |
| 类目[WOS] | Cell Biology |
| 关键词[WOS] | BREAST-CANCER CELLS ; FREQUENT EPIGENETIC INACTIVATION ; REPULSIVE AXON GUIDANCE ; MESENCHYMAL TRANSITION ; BETA-CATENIN ; ROUNDABOUT RECEPTOR ; TUMOR ANGIOGENESIS ; DOWN-REGULATION ; IN-VIVO ; ADHESION |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000289230800008 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/780]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Zhou, WJ,Geng, ZH,Chi, S,et al. Slit-Robo signaling induces malignant transformation through Hakai-mediated E-cadherin degradation during colorectal epithelial cell carcinogenesis[J]. CELL RESEARCH,2011,21(4):609-626. |
| APA | Zhou, WJ.,Geng, ZH.,Chi, S.,Zhang, WL.,Niu, XF.,...&Geng, JG.(2011).Slit-Robo signaling induces malignant transformation through Hakai-mediated E-cadherin degradation during colorectal epithelial cell carcinogenesis.CELL RESEARCH,21(4),609-626. |
| MLA | Zhou, WJ,et al."Slit-Robo signaling induces malignant transformation through Hakai-mediated E-cadherin degradation during colorectal epithelial cell carcinogenesis".CELL RESEARCH 21.4(2011):609-626. |
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