An novel inhibitor of TGF-β type I receptor, IN-1130, blocks breast cancer lung metastasis through inhibition of epithelial-mesenchymal transition

Cancer Letters

Volumn 351, Issue 1, 2014, Pages 72-80

  Park, Chul Yong ^a   Min, Kyung Nan ^a   Son, Jee Yeon ^a   Park, So Yeon ^a   Nam, Jeong Seok ^b   Kim, Dae Kee ^a   Sheen, Yhun Yhong ^a  

^a Ewha Womans University   (South Korea)

^b Gachon University   (South Korea)

Author keywords

ALK5; Breast cancer; IN 1130; Metastasis; Transforming growth factor (TGF )

Indexed keywords

ANTINEOPLASTIC AGENT; GELATINASE A; GELATINASE B; IN 1130; SMAD2 PROTEIN; TRANSFORMING GROWTH FACTOR BETA; TRANSFORMING GROWTH FACTOR BETA RECEPTOR 1; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; BREAST CANCER; CANCER SURVIVAL; CELL MIGRATION; CELL MOTILITY; CELL STRUCTURE; CELL TRANSPORT; CONTROLLED STUDY; DRUG EFFECT; DRUG MECHANISM; EPITHELIAL MESENCHYMAL TRANSITION; FEMALE; HUMAN; HUMAN CELL; LUNG METASTASIS; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; SURVIVAL RATE; TRANSCRIPTION INITIATION; TUMOR INVASION;

MUS; MUS MUSCULUS;

ALK5; BREAST CANCER; IN-1130; METASTASIS; TRANSFORMING GROWTH FACTOR-Β (TGF-Β);

ANIMALS; CELL LINE, TUMOR; CELL MOVEMENT; CELL NUCLEUS; DRUG SCREENING ASSAYS, ANTITUMOR; EPITHELIAL-MESENCHYMAL TRANSITION; FEMALE; HUMANS; IMIDAZOLES; LUNG; LUNG NEOPLASMS; MAMMARY NEOPLASMS, EXPERIMENTAL; MICE; MICE, INBRED BALB C; NEOPLASM INVASIVENESS; NEOPLASM TRANSPLANTATION; PROTEIN TRANSPORT; PROTEIN-SERINE-THREONINE KINASES; QUINOXALINES; RECEPTORS, TRANSFORMING GROWTH FACTOR BETA; TRANSFORMING GROWTH FACTOR BETA; TUMOR BURDEN;

EID: 84903696303     PISSN: 03043835     EISSN: 18727980     Source Type: Journal    
DOI: 10.1016/j.canlet.2014.05.006     Document Type: Article

References (26)

1. Hinestrosa M.C., Dickersin K., Klein P., Mayer M., Noss K., Slamon D., Sledge G., Visco F.M. Shaping the future of biomarker research in breast cancer to ensure clinical relevance. Nat. Rev. Cancer 2007, 7:309-315.
2. Eccles S.A., Welch D.R. Metastasis: recent discoveries and novel treatment strategies. Lancet 2007, 369:1742-1757.
3. Kang Y., Massague J. Epithelial-mesenchymal transitions: twist in development and metastasis. Cell 2004, 118:277-279.
4. Valcourt U., Kowanetz M., Niimi H., Heldin C.H., Moustakas A. TGF-beta and the Smad signaling pathway support transcriptomic reprogramming during epithelial-mesenchymal cell transition. Mol. Biol. Cell 2005, 16:1987-2002.
5. Deckers M., van Dinther M., Buijs J., Que I., Lowik C., van der Pluijm G., ten Dijke P. The tumor suppressor Smad4 is required for transforming growth factor beta-induced epithelial to mesenchymal transition and bone metastasis of breast cancer cells. Cancer Res. 2006, 66:2202-2209.
6. Katsuno Y., Hanyu A., Kanda H., Ishikawa Y., Akiyama F., Iwase T., Ogata E., Ehata S., Miyazono K., Imamura T. Bone morphogenetic protein signaling enhances invasion and bone metastasis of breast cancer cells through Smad pathway. Oncogene 2008, 27:6322-6333.
7. Saunier E.F., Akhurst R.J. TGF beta inhibition for cancer therapy. Curr. Cancer Drug Targets 2006, 6:565-578.
8. Schlingensiepen K.H., Fischer-Blass B., Schmaus S., Ludwig S. Antisense therapeutics for tumor treatment: the TGF-beta2 inhibitor AP 12009 in clinical development against malignant tumors. Recent Results Cancer Res. 2008, 177:137-150.
9. Yang Y.A., Dukhanina O., Tang B., Mamura M., Letterio J.J., MacGregor J., Patel S.C., Khozin S., Liu Z.Y., Green J., Anver M.R., Merlino G., Wakefield L.M. Lifetime exposure to a soluble TGF-beta antagonist protects mice against metastasis without adverse side effects. J. Clin. Invest. 2002, 109:1607-1615.
10. Nam J.S., Terabe M., Mamura M., Kang M.J., Chae H., Stuelten C., Kohn E., Tang B., Sabzevari H., Anver M.R., Lawrence S., Danielpour D., Lonning S., Berzofsky J.A., Wakefield L.M. An anti-transforming growth factor beta antibody suppresses metastasis via cooperative effects on multiple cell compartments. Cancer Res. 2008, 68:3835-3843.
11. Mohammad K.S., Javelaud D., Fournier P.G., Niewolna M., McKenna C.R., Peng X.H., Duong V., Dunn L.K., Mauviel A., Guise T.A. TGF-beta-RI kinase inhibitor SD-208 reduces the development and progression of melanoma bone metastases. Cancer Res. 2011, 71:175-184.
12. Bhola N.E., Balko J.M., Dugger T.C., Kuba M.G., Sanchez V., Sanders M., Stanford J., Cook R.S., Arteaga C.L. TGF-beta inhibition enhances chemotherapy action against triple-negative breast cancer. J. Clin. Invest. 2013, 123:1348-1358.
13. Moon J.A., Kim H.T., Cho I.S., Sheen Y.Y., Kim D.K. IN-1130, a novel transforming growth factor-beta type I receptor kinase (ALK5) inhibitor, suppresses renal fibrosis in obstructive nephropathy. Kidney Int. 2006, 70:1234-1243.
14. Lee G.T., Hong J.H., Mueller T.J., Watson J.A., Kwak C., Sheen Y.Y., Kim D.K., Kim S.J., Kim I.Y. Effect of IN-1130, a small molecule inhibitor of transforming growth factor-beta type I receptor/activin receptor-like kinase-5, on prostate cancer cells. J. Urol. 2008, 180:2660-2667.
15. Jonk L.J., Itoh S., Heldin C.H., ten Dijke P., Kruijer W. Identification and functional characterization of a Smad binding element (SBE) in the JunB promoter that acts as a transforming growth factor-beta, activin, and bone morphogenetic protein-inducible enhancer. J. Biol. Chem. 1998, 273:21145-21152.
16. Park C.Y., Son J.Y., Jin C.H., Nam J.S., Kim D.K., Sheen Y.Y. EW-7195, a novel inhibitor of ALK5 kinase inhibits EMT and breast cancer metastasis to lung. Eur. J. Cancer 2011, 47:2642-2653.
17. Joung K.E., Min K.N., An J.Y., Kim D.K., Kong G., Sheen Y.Y. Potent in vivo anti-breast cancer activity of IN-2001, a novel inhibitor of histone deacetylase, in MMTV/c-Neu mice. Cancer Res. 2006, 66:5394-5402.
18. Guy C.T., Webster M.A., Schaller M., Parsons T.J., Cardiff R.D., Muller W.J. Expression of the neu protooncogene in the mammary epithelium of transgenic mice induces metastatic disease. Proc. Natl. Acad. Sci. U. S. A. 1992, 89:10578-10582.
19. Bierie B., Moses H.L. Tumour microenvironment: TGFbeta: the molecular Jekyll and Hyde of cancer. Nat. Rev. Cancer 2006, 6:506-520.
20. Buck M.B., Knabbe C. TGF-beta signaling in breast cancer. Ann. N. Y. Acad. Sci. 2006, 1089:119-126.
21. Brown K.A., Pietenpol J.A., Moses H.L. A tale of two proteins: differential roles and regulation of Smad2 and Smad3 in TGF-beta signaling. J. Cell. Biochem. 2007, 101:9-33.
22. Hill C.S. Nucleocytoplasmic shuttling of Smad proteins. Cell Res. 2009, 19:36-46.
23. Koinuma D., Tsutsumi S., Kamimura N., Imamura T., Aburatani H., Miyazono K. Promoter-wide analysis of Smad4 binding sites in human epithelial cells. Cancer Sci. 2009, 100:2133-2142.
24. Ikushima H., Miyazono K. TGFbeta signalling: a complex web in cancer progression. Nat. Rev. Cancer 2010, 10:415-424.
25. Park C.Y., Kim D.K., Sheen Y.Y. 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 TGF-beta signaling in tumor suppression and cancer progression. Cancer Sci. 2011, 102:1889-1896.
26. Derynck R., Akhurst R.J., Balmain A. TGF-beta signaling in tumor suppression and cancer progression. Nat. Genet. 2001, 29:117-129.