EW-7203, a novel small molecule inhibitor of transforming growth factor-β (TGF-β) type I receptor/activin receptor-like kinase-5, blocks TGF-β1-mediated epithelial-to-mesenchymal transition in mammary epithelial cells

Cancer Science

Volumn 102, Issue 10, 2011, Pages 1889-1896

  Park, Chul Yong ^a   Kim, Dae Kee ^a   Sheen, Yhun Yhong ^a  

^a Ewha Womans University   (South Korea)

Author keywords

[No Author keywords available]

Indexed keywords

3 [[5 ([1,2,4]TRIAZOLO[1,5 A]PYRIDIN 6 YL) 4 (6 METHYLPYRIDIN 2 YL)THIAZOL 2 YLAMINO]METHYL]BENZONITRILE; ANTINEOPLASTIC AGENT; EW 7203; SMAD2 PROTEIN; TRANSFORMING GROWTH FACTOR BETA RECEPTOR 1; UNCLASSIFIED DRUG; 3 ((5 ((1,2,4)TRIAZOLO(1,5 A)PYRIDIN 6 YL) 4 (6 METHYLPYRIDIN 2 YL)THIAZOL 2 YLAMINO)METHYL)BENZONITRILE; 3-((5-((1,2,4)TRIAZOLO(1,5-A)PYRIDIN-6-YL)-4-(6-METHYLPYRIDIN-2-YL)THIAZOL-2-YLA MINO)METHYL)BENZONITRILE; PROTEIN SERINE THREONINE KINASE; PYRIDINE DERIVATIVE; SMAD PROTEIN; TGF BETA TYPE I RECEPTOR; TGF-BETA TYPE I RECEPTOR; THIAZOLE DERIVATIVE; TRANSFORMING GROWTH FACTOR BETA; TRANSFORMING GROWTH FACTOR BETA RECEPTOR;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BREAST CANCER; BREAST EPITHELIUM; CANCER CELL; CANCER INHIBITION; CELL ASSAY; CONFOCAL MICROSCOPY; CONTROLLED STUDY; DRUG EFFECT; EPITHELIAL MESENCHYMAL TRANSITION; FEMALE; HUMAN; HUMAN CELL; IC 50; IMMUNOBLOTTING; IN VIVO STUDY; LUNG METASTASIS; MALIGNANT TRANSFORMATION; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN LOCALIZATION; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION; TRANSCRIPTION INITIATION; TUMOR XENOGRAFT; WOUND HEALING; ANIMAL; BAGG ALBINO MOUSE; CELL TRANSFORMATION; DRUG ANTAGONISM; DRUG SCREENING; EPITHELIUM CELL; LUNG TUMOR; MAMMARY GLAND; METABOLISM; METASTASIS; TUMOR CELL LINE; UDDER;

ANIMALS; CELL LINE, TUMOR; CELL TRANSFORMATION, NEOPLASTIC; EPITHELIAL CELLS; EPITHELIAL-MESENCHYMAL TRANSITION; FEMALE; HUMANS; LUNG NEOPLASMS; MAMMARY GLANDS, ANIMAL; MAMMARY GLANDS, HUMAN; MICE; MICE, INBRED BALB C; NEOPLASM METASTASIS; PROTEIN-SERINE-THREONINE KINASES; PYRIDINES; RECEPTORS, TRANSFORMING GROWTH FACTOR BETA; SIGNAL TRANSDUCTION; SMAD PROTEINS; THIAZOLES; TRANSFORMING GROWTH FACTOR BETA; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84863011208     PISSN: 13479032     EISSN: 13497006     Source Type: Journal    
DOI: 10.1111/j.1349-7006.2011.02014.x     Document Type: Article

References (34)

1. Weigelt B, Peterse JL, van't Veer LJ. Breast cancer metastasis: markers and models. Nat Rev Cancer 2005; 5: 591-602.
2. Gupta GP, Massague J. Cancer metastasis: building a framework. Cell 2006; 127: 679-95.
3. Gorsch SM, Memoli VA, Stukel TA, Gold LI, Arrick BA. Immunohistochemical staining for transforming growth factor beta 1 associates with disease progression in human breast cancer. Cancer Res 1992; 52: 6949-52.
4. Ivanovic V, Todorovic-Rakovic N, Demajo M et al. Elevated plasma levels of transforming growth factor-beta 1 (TGF-beta 1) in patients with advanced breast cancer: association with disease progression. Eur J Cancer 2003; 39: 454-61.
5. Buck MB, Knabbe C. TGF-beta signaling in breast cancer. Ann N Y Acad Sci 2006; 1089: 119-26.
6. Muraoka-Cook RS, Shin I, Yi JY et al. Activated type I TGFbeta receptor kinase enhances the survival of mammary epithelial cells and accelerates tumor progression. Oncogene 2006; 25: 3408-23.
7. Massague J. TGFbeta in cancer. Cell 2008; 134: 215-30.
8. Tomaskovic-Crook E, Thompson EW, Thiery JP. Epithelial to mesenchymal transition and breast cancer. Breast Cancer Res 2009; 11: 213.
9. Yang J, Weinberg RA. Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Dev Cell 2008; 14: 818-29.
10. Brown KA, Pietenpol JA, Moses HL. A tale of two proteins: differential roles and regulation of Smad2 and Smad3 in TGF-beta signaling. J Cell Biochem 2007; 101: 9-33.
11. Shi Y, Massague J. Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell 2003; 113: 685-700.
12. Derynck R, Zhang YE. Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature 2003; 425: 577-84.
13. Yu L, Hebert MC, Zhang YE. TGF-beta receptor-activated p38 MAP kinase mediates Smad-independent TGF-beta responses. EMBO J 2002; 21: 3749-59.
14. Pennison M, Pasche B. Targeting transforming growth factor-beta signaling. Curr Opin Oncol 2007; 19: 579-85.
15. Halder SK, Beauchamp RD, Datta PK. A specific inhibitor of TGF-beta receptor kinase, SB-431542, as a potent antitumor agent for human cancers. Neoplasia 2005; 7: 509-21.
16. Ge R, Rajeev V, Ray P et al. Inhibition of growth and metastasis of mouse mammary carcinoma by selective inhibitor of transforming growth factor-beta type I receptor kinase in vivo. Clin Cancer Res 2006; 12: 4315-30.
17. Rausch MP, Hahn T, Ramanathapuram L et al. An orally active small molecule TGF-beta receptor I antagonist inhibits the growth of metastatic murine breast cancer. Anticancer Res 2009; 29: 2099-109.
18. Nam JS, Terabe M, Mamura M et al. An anti-transforming growth factor beta antibody suppresses metastasis via cooperative effects on multiple cell compartments. Cancer Res 2008; 68: 3835-43.
19. Zhao BM, Hoffmann FM. Inhibition of transforming growth factor-beta1-induced signaling and epithelial-to-mesenchymal transition by the Smadbinding peptide aptamer Trx-SARA. Mol Biol Cell 2006; 17: 3819-31.
20. Workman P, Aboagye EO, Balkwill F et al. Guidelines for the welfare and use of animals in cancer research. Br J Cancer 2010; 102: 1555-77.
21. Kataoka M, Schumacher G, Cristiano RJ et al. An agent that increases tumor suppressor transgene product coupled with systemic transgene delivery inhibits growth of metastatic lung cancer in vivo. Cancer Res 1998; 58: 4761-5.
22. Guarino M, Rubino B, Ballabio G. The role of epithelial-mesenchymal transition in cancer pathology. Pathology 2007; 39: 305-18.
23. Saunier EF, Akhurst RJ. TGF beta inhibition for cancer therapy. Curr Cancer Drug Targets 2006; 6: 565-78.
24. Hjelmeland MD, Hjelmeland AB, Sathornsumetee S et al. SB-431542, a small molecule transforming growth factor-beta-receptor antagonist, inhibits human glioma cell line proliferation and motility. Mol Cancer Ther 2004; 3: 737-45.
25. Subramanian G, Schwarz RE, Higgins L et al. Targeting endogenous transforming growth factor beta receptor signaling in SMAD4-deficient human pancreatic carcinoma cells inhibits their invasive phenotype1. Cancer Res 2004; 64: 5200-11.
26. Uhl M, Aulwurm S, Wischhusen J et al. SD-208, a novel transforming growth factor beta receptor I kinase inhibitor, inhibits growth and invasiveness and enhances immunogenicity of murine and human glioma cells in vitro and in vivo. Cancer Res 2004; 64: 7954-61.
27. Yi JY, Shin I, Arteaga CL. Type I transforming growth factor beta receptor binds to and activates phosphatidylinositol 3-kinase. J Biol Chem 2005; 280: 10870-6.
28. Yingling JM, Blanchard KL, Sawyer JS. Development of TGF-beta signalling inhibitors for cancer therapy. Nat Rev Drug Discov 2004; 3: 1011-22.
29. Ge R, Rajeev V, Subramanian G et al. Selective inhibitors of type I receptor kinase block cellular transforming growth factor-beta signaling. Biochem Pharmacol 2004; 68: 41-50.
30. Thiery JP. Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2002; 2: 442-54.
31. Oft M, Heider KH, Beug H. TGFbeta signaling is necessary for carcinoma cell invasiveness and metastasis. Curr Biol 1998; 8: 1243-52.
32. Cui W, Fowlis DJ, Bryson S et al. TGFbeta1 inhibits the formation of benign skin tumors, but enhances progression to invasive spindle carcinomas in transgenic mice. Cell 1996; 86: 531-42.
33. Kang Y, Massague J. Epithelial-mesenchymal transitions: twist in development and metastasis. Cell 2004; 118: 277-9.
34. Valcourt U, Kowanetz M, Niimi H, Heldin CH, Moustakas A. TGF-beta and the Smad signaling pathway support transcriptomic reprogramming during epithelial-mesenchymal cell transition. Mol Biol Cell 2005;16:1987-2002.