SLITs suppress tumor growth in vivo by silencing Sdf1/Cxcr4 within breast epithelium. Export

@article{citeulike:3563361, abstract = {The genes encoding Slits and their Robo receptors are silenced in many types of cancer, including breast, suggesting a role for this signaling pathway in suppressing tumorigenesis. The molecular mechanism underlying these tumor-suppressive effects has not been delineated. Here, we show that loss of Slits, or their Robo1 receptor, in murine mammary gland or human breast carcinoma cells results in coordinate up-regulation of the Sdf1 and Cxcr4 signaling axis, specifically within mammary epithelium. This is accompanied by hyperplastic changes in cells and desmoplastic alterations in the surrounding stroma. A similar inverse correlation between Slit and Cxcr4 expression is identified in human breast tumor tissues. Furthermore, we show in a xenograft model that Slit overexpression down-regulates CXCR4 and dominantly suppresses tumor growth. These studies classify Slits as negative regulators of Sdf1 and Cxcr4 and identify a molecular signature in hyperplastic breast lesions that signifies inappropriate up-regulation of key prometastatic genes.}, author = {Marlow, R. and Strickland, P. and Lee, J. S. and Wu, X. and Pebenito, M. and Binnewies, M. and Le, E. K. and Moran, A. and Macias, H. and Cardiff, R. D. and Sukumar, S. and Hinck, L.}, citeulike-article-id = {3563361}, citeulike-linkout-0 = {http://dx.doi.org/10.1158/0008-5472.CAN-08-1357}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18829537}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18829537}, day = {1}, doi = {10.1158/0008-5472.CAN-08-1357}, issn = {1538-7445}, journal = {Cancer research}, keywords = {reference, robo4, slit2}, month = {October}, number = {19}, pages = {7819--7827}, posted-at = {2008-11-18 00:05:11}, priority = {2}, title = {SLITs suppress tumor growth in vivo by silencing Sdf1/Cxcr4 within breast epithelium.}, url = {http://dx.doi.org/10.1158/0008-5472.CAN-08-1357}, volume = {68}, year = {2008} }

TY - JOUR ID - citeulike:3563361 L3 - citeulike-article-id:3563361 N2 - The genes encoding Slits and their Robo receptors are silenced in many types of cancer, including breast, suggesting a role for this signaling pathway in suppressing tumorigenesis. The molecular mechanism underlying these tumor-suppressive effects has not been delineated. Here, we show that loss of Slits, or their Robo1 receptor, in murine mammary gland or human breast carcinoma cells results in coordinate up-regulation of the Sdf1 and Cxcr4 signaling axis, specifically within mammary epithelium. This is accompanied by hyperplastic changes in cells and desmoplastic alterations in the surrounding stroma. A similar inverse correlation between Slit and Cxcr4 expression is identified in human breast tumor tissues. Furthermore, we show in a xenograft model that Slit overexpression down-regulates CXCR4 and dominantly suppresses tumor growth. These studies classify Slits as negative regulators of Sdf1 and Cxcr4 and identify a molecular signature in hyperplastic breast lesions that signifies inappropriate up-regulation of key prometastatic genes. IS - 19 JF - Cancer research SN - 1538-7445 EP - 7827 TI - SLITs suppress tumor growth in vivo by silencing Sdf1/Cxcr4 within breast epithelium. VL - 68 SP - 7819 KW - reference KW - robo4 KW - slit2 AU - Marlow, R AU - Strickland, P AU - Lee, JS AU - Wu, X AU - Pebenito, M AU - Binnewies, M AU - Le, EK AU - Moran, A AU - Macias, H AU - Cardiff, RD AU - Sukumar, S AU - Hinck, L PY - 2008/10/01/ UR - http://dx.doi.org/10.1158/0008-5472.CAN-08-1357 ER -