Regular Article |
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A reporter gene system for screening inhibitors of Wnt signaling pathway |
Xing-Yao LIa,b, Yuan-Yuan WANGa,c, Chun-Mao YUANa, Xiao-Jiang HAOa, Yan LIa |
a State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, China; b University of Chinese Academy of Sciences, Beijing 100049, China; c School of Marine Science and Technology, Harbin Institute of Technology at Weihai, Shandong 264209, China |
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Abstract Abnormal activation of canonical Wnt signaling has been associated with various types of cancer. Inhibitory reagents targeting the Wnt signaling have great potential to inhibit the growth of relevant tumors. Here we generated a cell-based screening strategy for identification of antagonists of the Wnt/β-catenin signaling pathway. Stable expression wnt3a was generated in HEK293 cell line, which harbors dual-luciferase reporters. The Wnt signaling in the stably transfected cell line was proved to be very sensitive to (-)-epigallocatechin-3-gallate (EGCG) and lithium chloride (LiCl) treatment, respectively. Natural compounds were screened and a couple of novel inhibitory modulators of the Wnt signaling pathway were obtained.
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Keywords
Wnt signaling
natural compounds
dual-luciferase reporter
tumor
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Fund:We thank Dr. B. Mao for TopFlash and renilla plasmids, and Dr. H. Zhou for scientific and technological comments and advice on the manuscript. This project was supported financially by the hundreds top talents program awarded to Yan Li from the Chinese Academy of Sciences, the Major State Basic Research Development Program of China (No. 2009CB522300), the NSFC (No.81173076), and the project of recruited top talent of sciences and technology of Yunnan Province (2009C1120). |
Issue Date: 11 February 2018
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[1] |
Muller, J. M.; Chevrier, L.; Cochaud, S.; Meunier, A. C.; Chadeneau, C. Drug Discov. Today Dis. Mech. 2007, 4, 285-291.
|
[2] |
Klaus, A.; Birchmeier, W. Nat. Rev. Cancer 2008, 8, 387-398.
|
[3] |
Clevers, H.; Nusse, R. Cell 2012, 149, 1192-1205.
|
[4] |
de Sousa, E. M.; Vermeulen, L.; Richel, D.; Medema, J. P. Clin. Cancer Res. 2011, 17, 647-653.
|
[5] |
van Es, J. H.; Jay, P.; Gregorieff, A.; van Gijn, M. E.; Jonkheer, S.; Hatzis, P.; Thiele, A.; van den Born, M.; Begthel, H.; Brabletz, T.; Taketo, M. M.; Clevers, H. Nat. Cell Biol. 2005, 7, 381-386.
|
[6] |
Brabletz, T.; Jung, A.; Dag, S.; Hlubek, F.; Kirchner, T. Am. J. Pathol. 1999, 155, 1033-1038.
|
[7] |
Ceballos, M. P.; Parody, J. P.; Alvarez Mde, L.; Ingaramo, P. I.; Carnovale, C. E.; Carrillo, M. C. Biochem. Pharmacol. 2011, 82, 1682-1691.
|
[8] |
Wang, Y.; Krivtsov, A. V.; Sinha, A. U.; North, T. E.; Goessling, W.; Feng, Z.; Zon, L. I.; Armstrong, S. A. Science 2010, 327, 1650-1653.
|
[9] |
Lu, D.; Zhao, Y.; Tawatao, R.; Cottam, H. B.; Sen, M.; Leoni, L. M.; Kipps, T. J.; Corr, M.; Carson, D. A. Proc. Natl. Acad. Sci. U. S. A. 2004, 101, 3118-3123.
|
[10] |
Chien, A. J.; Moore, E. C.; Lonsdorf, A. S.; Kulikauskas, R. M.; Rothberg, B. G.; Berger, A. J.; Major, M. B.; Hwang, S. T.; Rimm, D. L.; Moon, R. T. Proc. Natl. Acad. Sci. U. S. A. 2009, 106, 1193-1198.
|
[11] |
Wang, L.; Heidt, D. G.; Lee, C. J.; Yang, H.; Logsdon, C. D.; Zhang, L.; Fearon, E. R.; Ljungman, M.; Simeone, D. M. Cancer Cell 2009, 15, 207-219.
|
[12] |
Vaira, S.; Friday, E.; Scott, K.; Conrad, S.; Turturro, F. J. Cell Physiol. 2012, 227, 578-586.
|
[13] |
Ilyas, M.; Tomlinson, I. P.; Rowan, A.; Pignatelli, M.; Bodmer, W. F. Proc. Natl. Acad. Sci. U. S. A. 1997, 94, 10330-10334.
|
[14] |
Kim, J.; Zhang, X.; Rieger-Christ, K. M.; Summerhayes, I. C.; Wazer, D. E.; Paulson, K. E.; Yee, A. S. J. Biol. Chem. 2006, 281, 10865-10875.
|
[15] |
Shtutman, M.; Zhurinsky, J.; Simcha, I.; Albanese, C.; D'Amico, M.; Pestell, R.; Ben-Ze'ev, A. Proc. Natl. Acad. Sci. U. S. A. 1999, 96, 5522-5527.
|
[16] |
Tetsu, O.; McCormick, F. Nature 1999, 398, 422-426.
|
[17] |
Itokawa, H.; Qiao, Z. S.; Hirobe, C.; Takeya, K. Chem. Pharm. Bull. 1995, 43, 1171-1175.
|
[18] |
Cragg, G. M.; Grothaus, P. G.; Newman, D. J. Chem. Rev. 2009, 109, 3012-3043.
|
[19] |
Newman, D. J.; Cragg, G. M. J. Nat. Prod. 2012, 75, 311-335.
|
[20] |
Thorne, N.; Inglese, J.; Auld, D. S. Chem. Biol. 2010, 17, 646-657.
|
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