Abstract

The Slit family of migratory cues is secreted by midline cells, endothelial cells and cancer cells. They bind to a family of cell-surface transmembrane proteins, Roundabout (Robo), and act as repellants for axon guidance and neuronal migration, endogenous inhibitors for leukocyte chemotaxis and chemoattractants for vascular endothelial cells. To assess the pathological significance and to elucidate the underlying molecular mechanisms for Slit-Robo signaling in the growth and metastasis of tumors, we will investigate (1) the effect of Slit-Robo signaling in lymphangiogenesis and lymphatic metastasis, the pathological role of Slit2 in tumor angiogenesis and growth and (2) the effect of Slit-Robo signaling on canonical Wnt signaling. We believe that these studies will not only deepen our understanding of the molecular mechanisms involved in tumor growth and metastasis, but also facilitate the use of Slit2 and Robo1 as the novel molecular targets for diagnosis and treatment of cancers.

Public Health Relevance

Our study on Slit-Robo signaling in tumor growth and metastasis will not only deepen our understanding of the molecular mechanisms involved in tumor growth and metastasis, but also facilitate the use of Slit2 and Robo1 as the novel molecular targets of diagnosis and treatment of cancers.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA126897-05
Application #
8515748
Study Section
Tumor Microenvironment Study Section (TME)
Program Officer
Woodhouse, Elizabeth
Project Start
2009-01-01
Project End
2013-11-30
Budget Start
2012-12-01
Budget End
2013-11-30
Support Year
5
Fiscal Year
2013
Total Cost
$294,205
Indirect Cost
$105,006

  Institution

Name
University of Michigan Ann Arbor
Department
Biology
Type
Schools of Dentistry
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109

  Publications

Zhou, Wei-Jie; Geng, Zhen H; Spence, Jason R et al. (2013) Induction of intestinal stem cells by R-spondin 1 and Slit2 augments chemoradioprotection. Nature 501:107-11
Ji, Zhe; Ke, Zun-Ji; Geng, Jian-Guo (2012) SAP suppresses the development of experimental autoimmune encephalomyelitis in C57BL/6 mice. Immunol Cell Biol 90:388-95
Ochoa-Alvarez, Jhon Alberto; Krishnan, Harini; Shen, Yongquan et al. (2012) Plant lectin can target receptors containing sialic acid, exemplified by podoplanin, to inhibit transformed cell growth and migration. PLoS One 7:e41845
Zhou, Wei-Jie; Geng, Zhen H; Chi, Shan et al. (2011) Slit-Robo signaling induces malignant transformation through Hakai-mediated E-cadherin degradation during colorectal epithelial cell carcinogenesis. Cell Res 21:609-26
Feng, Lifeng; Wang, Jin-Tao; Jin, Hongchuan et al. (2011) SH3KBP1-binding protein 1 prevents epidermal growth factor receptor degradation by the interruption of c-Cbl-CIN85 complex. Cell Biochem Funct 29:589-96
Huang, Zhi-Hui; Wang, Ying; Su, Zhi-da et al. (2011) Slit-2 repels the migration of olfactory ensheathing cells by triggering Ca2+-dependent cofilin activation and RhoA inhibition. J Cell Sci 124:186-97
Han, Hai-xiong; Geng, Jian-guo (2011) Over-expression of Slit2 induces vessel formation and changes blood vessel permeability in mouse brain. Acta Pharmacol Sin 32:1327-36
Nie, Jichan; Liu, Xishi; Zheng, Yu et al. (2011) Increased immunoreactivity to SLIT/ROBO1 and its correlation with severity of dysmenorrhea in adenomyosis. Fertil Steril 95:1164-7
Wang, L-J; Zhou, X; Wang, W et al. (2011) Andrographolide inhibits oral squamous cell carcinogenesis through NF-?B inactivation. J Dent Res 90:1246-52
Yang, Xiao-Mei; Han, Hai-Xiong; Sui, Fei et al. (2010) Slit-Robo signaling mediates lymphangiogenesis and promotes tumor lymphatic metastasis. Biochem Biophys Res Commun 396:571-7

Showing the most recent 10 out of 13 publications