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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA126897-04
Application #
7996017
Study Section
Tumor Microenvironment Study Section (TME)
Program Officer
Woodhouse, Elizabeth
Project Start
2009-01-01
Project End
2013-11-30
Budget Start
2011-12-01
Budget End
2012-11-30
Support Year
4
Fiscal Year
2012
Total Cost
$313,325
Indirect Cost
$105,825
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
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
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
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
Ye, Bu-Qing; Geng, Zhen H; Ma, Li et al. (2010) Slit2 regulates attractive eosinophil and repulsive neutrophil chemotaxis through differential srGAP1 expression during lung inflammation. J Immunol 185:6294-305
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
Ma, Shulan; Liu, Xishi; Geng, Jian-Guo et al. (2010) Increased SLIT immunoreactivity as a biomarker for recurrence in endometrial carcinoma. Am J Obstet Gynecol 202:68.e1-68.e11
Shen, Fanghua; Liu, Xishi; Geng, Jian-Guo et al. (2009) Increased immunoreactivity to SLIT/ROBO1 in ovarian endometriomas: a likely constituent biomarker for recurrence. Am J Pathol 175:479-88