Activation of Robo1 signaling of breast cancer cells by Slit2 from stromal fibroblast restrains tumorigenesis via blocking PI3K/Akt/β-catenin pathway

Cancer Research

Volumn 72, Issue 18, 2012, Pages 4652-4661

  Chang, Po Hao ^a   Hwang Verslues, Wendy W ^b   Chang, Yi Cheng ^b   Chen, Chun Chin ^b   Hsiao, Michael ^b   Jeng, Yung Ming ^c   Chang, King Jen ^c,d   Lee, Eva Y H P ^e   Shew, Jin Yuh ^a,b   Lee, Wen Hwa ^e  

^a NATIONAL TAIWAN UNIVERSITY   (Taiwan)

^b GENOMICS RESEARCH CENTER   (Taiwan)

^c NATIONAL TAIWAN UNIVERSITY HOSPITAL   (Taiwan)

^d Cheng Chin General Hospital   (Taiwan)

^e UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BETA CATENIN; CYCLIN D1; MYC PROTEIN; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; ROUNDABOUT RECEPTOR; ROUNDABOUT RECEPTOR 1; SLIT2 PROTEIN; UNCLASSIFIED DRUG;

AKT SIGNALING PATHWAY; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BETA CATENIN SIGNALING PATHWAY; BREAST CANCER; CANCER CELL; CARCINOGENESIS; CELL HETEROGENEITY; CONTROLLED STUDY; DOWN REGULATION; ENZYME ACTIVATION; FIBROBLAST; GENE EXPRESSION PROFILING; GENE TRANSLOCATION; HUMAN; HUMAN CELL; HUMAN TISSUE; IMMUNOFLUORESCENCE; MOUSE; NONHUMAN; PI3K SIGNALING PATHWAY; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; SIGNAL TRANSDUCTION; TUMOR GROWTH; TUMOR MICROENVIRONMENT; TUMOR VOLUME;

ANIMALS; BETA CATENIN; BREAST NEOPLASMS; CELL LINE, TUMOR; DISEASE PROGRESSION; FEMALE; FIBROBLASTS; HUMANS; IMMUNOBLOTTING; IMMUNOHISTOCHEMISTRY; IMMUNOPRECIPITATION; INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS; MICE; MICE, INBRED NOD; MICE, SCID; NERVE TISSUE PROTEINS; PHOSPHATIDYLINOSITOL 3-KINASES; PROTO-ONCOGENE PROTEINS C-AKT; REAL-TIME POLYMERASE CHAIN REACTION; RECEPTORS, IMMUNOLOGIC; SIGNAL TRANSDUCTION; TUMOR MICROENVIRONMENT;

EID: 84866389516     PISSN: 00085472     EISSN: 15387445     Source Type: Journal    
DOI: 10.1158/0008-5472.CAN-12-0877     Document Type: Article

References (40)

1. Wiseman BS, Werb Z. Stromal effects on mammary gland development and breast cancer. Science 2002;296:1046-9.
2. Polyak K, Kalluri R. The role of the microenvironment in mammary gland development and cancer. Cold Spring Harb Perspect Biol 2010;2:a003244.
3. Sternlicht MD, Sunnarborg SW, Kouros-Mehr H, Yu Y, Lee DC, Werb Z. Mammary ductal morphogenesis requires paracrine activation of stromal EGFR via ADAM17-dependent shedding of epithelial amphiregulin. Development 2005;132:3923-33.
4. Daniel CW, Robinson S, Silberstein GB. The role of TGF-beta in patterning and growth of the mammary ductal tree. J Mammary Gland Biol Neoplasia 1996;1:331-41.
5. Liotta LA, Kohn EC. The microenvironment of the tumour-host interface. Nature 2001;411:375-9.
6. Kalluri R, Zeisberg M. Fibroblasts in cancer. Nat Rev Cancer 2006;6:392-401.
7. Bhowmick NA, Neilson EG, Moses HL. Stromal fibroblasts in cancer initiation and progression. Nature 2004;432:332-7.
8. Rong S, Bodescot M, Blair D, Dunn J, Nakamura T, Mizuno K, et al. Tumorigenicity of the met proto-oncogene and the gene for hepatocyte growth factor. Mol Cell Biol 1992;12:5152-8.
9. Tyan SW, Kuo WH, Huang CK, Pan CC, Shew JY, Chang KJ, et al. Breast cancer cells induce cancer-associated fibroblasts to secrete hepatocyte growth factor to enhance breast tumorigenesis. PLoS One 2011;6:e15313.
10. Orimo A, Gupta PB, Sgroi DC, Arenzana-Seisdedos F, Delaunay T, Naeem R, et al. Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell 2005;121:335-48.
11. Ma C, Rong Y, Radiloff DR, Datto MB, Centeno B, Bao S, et al. Extracellular matrix protein betaig-h3/TGFBI promotes metastasis of colon cancer by enhancing cell extravasation. Genes Dev 2008;22:308- 21.
12. Littlepage LE, Sternlicht MD, Rougier N, Phillips J, Gallo E, Yu Y, et al. Matrix metalloproteinases contribute distinct roles in neuroendocrine prostate carcinogenesis, metastasis, and angiogenesis progression. Cancer Res 2010;70:2224-34.
13. Woodruff M. The Hubert, Walter Lecture, 1982 - Interaction of Cancer and Host. Brit J Cancer 1982;46:313-22.
14. Bissell MJ, Hines WC. Why don't we get more cancer? A proposed role of the microenvironment in restraining cancer progression. Nat Med 2011;17:320-9.
15. Rich AR. On the frequency of occurrence of occult carcinoma of the prostrate. 1934. Int J Epidemiol 2007;36:274-7.
16. van de Vijver MJ, He YD, van't Veer LJ, Dai H, Hart AA, Voskuil DW, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med 2002;347:1999-2009.
17. Jones CA, London NR, Chen H, Park KW, Sauvaget D, Stockton RA, et al. Robo4 stabilizes the vascular network by inhibiting pathologic angiogenesis and endothelial hyperpermeability. Nat Med 2008;14:448- 53.
18. Ghosh S, Ghosh A, Maiti GP, Alam N, Roy A, Roychoudhury S, et al. Alterations of ROBO1/DUTT1 and ROBO2 loci in early dysplastic lesions of head and neck: clinical and prognostic implications. Hum Genet 2009;125:189-98.
19. Brose K, Bland KS, Wang KH, Arnott D, Henzel W, Goodman CS, et al. Slit proteins bind Robo receptors and have an evolutionarily conserved role in repulsive axon guidance. Cell 1999;96:795-806.
20. Kidd T, Bland KS, Goodman CS. Slit is the midline repellent for the robo receptor in Drosophila. Cell 1999;96:785-94.
21. Macias H, Moran A, Samara Y, Moreno M, Compton JE, Harburg G, et al. SLIT/ROBO1 signaling suppresses mammary branching morphogenesis by limiting basal cell number. Dev Cell 2011;20:827-40.
22. Tseng RC, Lee SH, Hsu HS, Chen BH, Tsai WC, Tzao C, et al. SLIT2 attenuation during lung cancer progression deregulates beta-catenin and E-cadherin and associates with poor prognosis. Cancer Res 2010;70:543-51.
23. Fry MJ. Phosphoinositide 3-kinase signalling in breast cancer: how big a role might it play? Breast Cancer Res 2001;3:304-12.
24. Sun M, Paciga JE, Feldman RI, Yuan Z, Coppola D, Lu YY, et al. Phosphatidylinositol-3-OH Kinase (PI3K)/AKT2, activated in breast cancer, regulates and is induced by estrogen receptor alpha (ERalpha) via interaction between ERalpha and PI3K. Cancer Res 2001;61:5985- 91.
25. Moses LE, Shapiro D, Littenberg B. Combining independent studies of a diagnostic test into a summary ROC curve: data-analytic approaches and some additional considerations. Stat Med 1993;12:1293-316.
26. Finak G, Bertos N, Pepin F, Sadekova S, Souleimanova M, Zhao H, et al. Stromal gene expression predicts clinical outcome in breast cancer. Nat Med 2008;14:518-27.
27. Mueller MM, Fusenig NE. Friends or foes - bipolar effects of the tumour stroma in cancer. Nat Rev Cancer 2004;4:839-49.
28. Tessier-Lavigne M, Goodman CS. The molecular biology of axon guidance. Science 1996;274:1123-33.
29. Sundaresan V, Chung G, Heppell-Parton A, Xiong J, Grundy C, Roberts I, et al. Homozygous deletions at 3p12 in breast and lung cancer. Oncogene 1998;17:1723-9.
30. Dallol A, Forgacs E, Martinez A, Sekido Y, Walker R, Kishida T, et al. Tumour specific promoter region methylation of the human homologue of the Drosophila Roundabout gene DUTT1 (ROBO1) in human cancers. Oncogene 2002;21:3020-8.
31. Brantley-Sieders DM, Dunaway CM, Rao M, Short S, Hwang Y, Gao Y, et al. Angiocrine factors modulate tumor proliferation and motility through EphA2 repression of Slit2 tumor suppressor function in endothelium. Cancer Res 2011;71:976-87.
32. Alajez NM, Lenarduzzi M, Ito E, Hui AB, Shi W, Bruce J, et al. MiR-218 suppresses nasopharyngeal cancer progression through downregulation of survivin and the SLIT2-ROBO1 pathway. Cancer Res 2011;71:2381- 91.
33. Cantley LC, Neel BG. New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway. Proc Natl Acad Sci U S A 1999;96:4240-5.
34. Satyamoorthy K, Li G, Vaidya B, Patel D, Herlyn M. Insulin-like growth factor-1 induces survival and growth of biologically early melanoma cells through both the mitogen-activated protein kinase and betacatenin pathways. Cancer Res 2001;61:7318-24.
35. Prasad A, Paruchuri V, Preet A, Latif F, Ganju RK. Slit-2 induces a tumor-suppressive effect by regulating beta-catenin in breast cancer cells. J Biol Chem 2008;283:26624-33.
36. Hu P, Margolis B, Skolnik EY, Lammers R, Ullrich A, Schlessinger J. Interaction of phosphatidylinositol 3-kinase-associated p85 with epidermal growth factor and platelet-derived growth factor receptors. Mol Cell Biol 1992;12:981-90.
37. Kononen J, Bubendorf L, Kallioniemi A, Barlund M, Schraml P, Leighton S, et al. Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med 1998;4:844-7.
38. Barbareschi M, Pelosio P, Caffo O, Buttitta F, Pellegrini S, Barbazza R, et al. Cyclin-D1-gene amplification and expression in breast carcinoma: relation with clinicopathologic characteristics and with retinoblastoma gene product, p53 and p21WAF1 immunohistochemical expression. Int J Cancer 1997;74:171-4.
39. Sharma M, Chuang WW, Sun Z. Phosphatidylinositol 3-kinase/Akt stimulates androgen pathway through GSK3beta inhibition and nuclear beta-catenin accumulation. J Biol Chem 2002;277:30935-41.
40. Samowitz WS, Powers MD, Spirio LN, Nollet F, van Roy F, Slattery ML. Beta-catenin mutations are more frequent in small colorectal adenomas than in larger adenomas and invasive carcinomas. Cancer Res 1999;59:1442-4.