Selective identification of hedgehog pathway antagonists by direct analysis of smoothened ciliary translocation

ACS Chemical Biology

Volumn 7, Issue 6, 2012, Pages 1040-1048

  Wang, Yu ^a,c,e   Arvanites, Anthony C ^a,b   Davidow, Lance ^a,b   Blanchard, Joel ^a,b,f   Lam, Kelvin ^a,b,g   Yoo, Jin Woo ^d   Coy, Shannon ^a,b,h   Rubin, Lee L ^a,b   McMahon, Andrew P ^a,b  

^a HARVARD UNIVERSITY   (United States)

^b HARVARD STEM CELL INSTITUTE   (United States)

^c HARVARD UNIVERSITY   (United States)

^d HARVARD COLLEGE   (United States)

^e MORGRIDGE INSTITUTE FOR RESEARCH   (United States)

^f SCRIPPS RESEARCH INSTITUTE   (United States)

^g Blue Sky Biotech Inc   (United States)

^h DARTMOUTH MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLOPAMINE; DY 131; FORSKOLIN; HYBRID PROTEIN; LIGAND; MEMBRANE PROTEIN; SMOOTHENED; SONIC HEDGEHOG PROTEIN; UNCLASSIFIED DRUG; VISMODEGIB;

ANIMAL CELL; ARTICLE; BINDING SITE; CELL PROLIFERATION; CONTROLLED STUDY; DOSE RESPONSE; HUMAN; HUMAN CELL; MUCOCILIARY TRANSPORT; NONHUMAN; PRIORITY JOURNAL; PROTEIN LOCALIZATION; SIGNAL TRANSDUCTION; TRANSCRIPTION INITIATION; WILD TYPE;

ANIMALS; ANTINEOPLASTIC AGENTS; CELL LINE; CILIA; HEDGEHOG PROTEINS; HUMANS; MICE; NEOPLASMS; PROTEIN TRANSPORT; RECEPTORS, G-PROTEIN-COUPLED; SIGNAL TRANSDUCTION;

EID: 84862582197     PISSN: 15548929     EISSN: 15548937     Source Type: Journal    
DOI: 10.1021/cb300028a     Document Type: Article

References (40)

1. McMahon, A. P., Ingham, P. W., and Tabin, C. J. (2003) Developmental roles and clinical significance of hedgehog signaling Curr. Top. Dev. Biol. 53, 1-114 (Pubitemid 137639458)
2. Xie, J., Murone, M., Luoh, S. M., Ryan, A., Gu, Q., Zhang, C., Bonifas, J. M., Lam, C. W., Hynes, M., Goddard, A., Rosenthal, A., Epstein, E. H., Jr., and de Sauvage, F. J. (1998) Activating Smoothened mutations in sporadic basal-cell carcinoma Nature 391, 90-92 (Pubitemid 28079221)
3. Romer, J. T., Kimura, H., Magdaleno, S., Sasai, K., Fuller, C., Baines, H., Connelly, M., Stewart, C. F., Gould, S., Rubin, L. L., and Curran, T. (2004) Suppression of the Shh pathway using a small molecule inhibitor eliminates medulloblastoma in Ptc1(±)p53(-/-) mice Cancer Cell 6, 229-240 (Pubitemid 39222036)
4. Yauch, R. L., Gould, S. E., Scales, S. J., Tang, T., Tian, H., Ahn, C. P., Marshall, D., Fu, L., Januario, T., Kallop, D., Nannini-Pepe, M., Kotkow, K., Marsters, J. C., Rubin, L. L., and de Sauvage, F. J. (2008) A paracrine requirement for hedgehog signalling in cancer Nature 455, 406-410
5. Rubin, L. L. and de Sauvage, F. J. (2006) Targeting the Hedgehog pathway in cancer Nat. Rev. Drug Discovery 5, 1026-1033 (Pubitemid 44835129)
6. Scales, S. and de Sauvage, F. (2009) Mechanisms of Hedgehog pathway activation in cancer and implications for therapy Trends Pharmacol. Sci. 6, 303-312
7. Von Hoff, D., Lorusso, P., Rudin, C., Reddy, J., Yauch, R., Tibes, R., Weiss, G., Borad, M., Hann, C., Brahmer, J., Mackey, H., Lum, B., Darbonne, W., Marsters, J., de Sauvage, F., and Low, J. (2009) Inhibition of the hedgehog pathway in advanced basal-cell carcinoma N. Engl. J. Med. 361, 1164-1172
8. Allison, M. (2012) Hedgehog hopes lifted by approval... and stung by failure Nat. Biotechnol. 30, 203
9. Corbit, K. C., Aanstad, P., Singla, V., Norman, A. R., Stainier, D. Y. R., and Reiter, J. F. (2005) Vertebrate Smoothened functions at the primary cilium Nature 437, 1018-1021 (Pubitemid 41486982)
10. Rohatgi, R., Milenkovic, L., and Scott, M. P. (2007) Patched1 regulates hedgehog signaling at the primary cilium Science 317, 372-376 (Pubitemid 47106377)
11. Wilson, C. W., Chen, M.-H., and Chuang, P.-T. (2009) Smoothened adopts multiple active and inactive conformations capable of trafficking to the primary cilium PLoS One 4, e5182
12. Rohatgi, R., Milenkovic, L., Corcoran, R., and Scott, M. (2009) Hedgehog signal transduction by Smoothened: Pharmacologic evidence for a 2-step activation process Proc. Natl. Acad. Sci. U.S.A. 106, 3196-3201
13. Wang, Y., Zhou, Z., Walsh, C., and McMahon, A. (2009) Selective translocation of intracellular Smoothened to the primary cilium in response to Hedgehog pathway modulation Proc. Natl. Acad. Sci. U.S.A. 106, 2623-2628
14. Dijkgraaf, G. J., Alicke, B., Weinmann, L., Januario, T., West, K., Modrusan, Z., Burdick, D., Goldsmith, R., Robarge, K., Sutherlin, D., Scales, S. J., Gould, S. E., Yauch, R. L., and de Sauvage, F. J. (2011) Small molecule inhibition of GDC-0449 refractory smoothened mutants and downstream mechanisms of drug resistance Cancer Res. 71, 435-444
15. Yauch, R., Dijkgraaf, G., Alicke, B., Januario, T., Ahn, C., Holcomb, T., Pujara, K., Stinson, J., Callahan, C., Tang, T., Bazan, J., Kan, Z., Seshagiri, S., Hann, C., Gould, S., Low, J., Rudin, C., and de Sauvage, F. (2009) Smoothened mutation confers resistance to a hedgehog pathway inhibitor in medulloblastoma Science 326, 572-574
16. Chen, J. K., Taipale, J., Young, K. E., Maiti, T., and Beachy, P. A. (2002) Small molecule modulation of Smoothened activity Proc. Natl. Acad. Sci. U.S.A. 99, 14071-14076 (Pubitemid 35257626)
17. Zhang, J. H., Chung, T. D. Y., and Oldenburg, K. R. (1999) A simple statistical parameter for use in evaluation and validation of high throughput screening assays J. Biomol. Screening 4, 67-73 (Pubitemid 29278954)
18. Hyman, J., Firestone, A., Heine, V., Zhao, Y., Ocasio, C., Han, K., Sun, M., Rack, P., Sinha, S., Wu, J., Solow-Cordero, D., Jiang, J., Rowitch, D., and Chen, J. (2009) Small-molecule inhibitors reveal multiple strategies for Hedgehog pathway blockade Proc. Natl. Acad. Sci. U.S.A. 106, 14132-14137
19. Jordan, M. A. and Wilson, L. (2004) Microtubules as a target for anticancer drugs Nat. Rev. Cancer 4, 253-265 (Pubitemid 38525281)
20. Brunton, S. A., Stibbard, J. H. A., Rubin, L. L., Kruse, L. I., Guicherit, O. M., Boyd, E. A., and Price, S. (2008) Potent inhibitors of the hedgehog signaling pathway J. Med. Chem. 51, 1108-1110 (Pubitemid 351480373)
21. Incardona, J. P. and Eaton, S. (2000) Cholesterol in signal transduction Curr. Opin. Cell Biol. 12, 193-203 (Pubitemid 30142566)
22. Lewis, P. M., Dunn, M. P., McMahon, J. A., Logan, M., Martin, J. F., St-Jacques, B., and McMahon, A. P. (2001) Cholesterol modification of sonic hedgehog is required for long-range signaling activity and effective modulation of signaling by Ptc1 Cell 105, 599-612 (Pubitemid 32524113)
23. Li, Y. N., Zhang, H. M., Litingtung, Y., and Chiang, C. (2006) Cholesterol modification restricts the spread of Shh gradient in the limb bud Proc. Natl. Acad. Sci. U.S.A. 103, 6548-6553
24. Cooper, M. K., Wassif, C. A., Krakowiak, P. A., Taipale, J., Gong, R., Kelley, R. I., Porter, F. D., and Beachy, P. A. (2003) A defective response to Hedgehog signaling in disorders of cholesterol biosynthesis Nat. Genet. 33, 508-513; correction vol 34, p 113 (Pubitemid 36390014)
25. Kim, J., Tang, J. Y., Gong, R., Lee, J. J., Clemons, K. V., Chong, C. R., Chang, K. S., Fereshteh, M., Gardner, D., Reya, T., Liu, J. O., Epstein, E. H., Stevens, D. A., and Beachy, P. A. (2010) Itraconazole, a commonly used antifungal that inhibits Hedgehog pathway activity and cancer growth Cancer Cell 17, 388-399
26. Yu, D. D. and Forman, B. M. (2005) Identification of an agonist ligand for estrogen-related receptors ERRbeta/gamma Bioorg. Med. Chem. Lett. 15, 1311-1313 (Pubitemid 40268982)
27. Zuercher, W. J., Gaillard, S., Orband-Miller, L. A., Chao, E. Y., Shearer, B. G., Jones, D. G., Miller, A. B., Collins, J. L., McDonnell, D. P., and Willson, T. M. (2005) Identification and structure-activity relationship of phenolic acyl hydrazones as selective agonists for the estrogen-related orphan nuclear receptors ERRbeta and ERRgamma J. Med. Chem. 48, 3107-3109 (Pubitemid 40628027)
28. Taipale, J., Chen, J. K., Cooper, M. K., Wang, B., Mann, R. K., Milenkovic, L., Scott, M. P., and Beachy, P. A. (2000) Effects of oncogenic mutations in Smoothened and Patched can be reversed by cyclopamine Nature 406, 1005-1009
29. Han, Y.-G., Spassky, N., Romaguera-Ros, M., Garcia-Verdugo, J.-M., Aguilar, A., Schneider-Maunoury, S., and Alvarez-Buylla, A. (2008) Hedgehog signaling and primary cilia are required for the formation of adult neural stem cells Nat. Neurosci. 11, 277-284 (Pubitemid 351311806)
30. Chen, J. K., Taipale, J., Cooper, M. K., and Beachy, P. A. (2002) Inhibition of Hedgehog signaling by direct binding of cyclopamine to Smoothened Genes Dev. 16, 2743-2748 (Pubitemid 35253140)
31. Lauth, M., Bergström, A., Shimokawa, T., and Toftgard, R. (2007) Inhibition of GLI-mediated transcription and tumor cell growth by small-molecule antagonists Proc. Natl. Acad. Sci. U.S.A. 104, 8455-8460 (Pubitemid 47175509)
32. Schuller, U., Heine, V. M., Mao, J., Kho, A. T., Dillon, A. K., Han, Y. G., Huillard, E., Sun, T., Ligon, A. H., Qian, Y., Ma, Q., Alvarez-Buylla, A., McMahon, A. P., Rowitch, D. H., and Ligon, K. L. (2008) Acquisition of granule neuron precursor identity is a critical determinant of progenitor cell competence to form Shh-induced medulloblastoma Cancer Cell 14, 123-134
33. Frank-Kamenetsky, M., Zhang, X. M., Bottega, S., Guicherit, O., Wichterle, H., Dudek, H., Bumcrot, D., Wang, F. Y., Jones, S., Shulok, J., Rubin, L. L., and Porter, J. A. (2002) Small-molecule modulators of Hedgehog signaling: identification and characterization of Smoothened agonists and antagonists J. Biol. 1, 10
34. Chen, Y., Sasai, N., Ma, G., Yue, T., Jia, J., Briscoe, J., and Jiang, J. (2011) Sonic Hedgehog dependent phosphorylation by CK1alpha and GRK2 is required for ciliary accumulation and activation of smoothened PLoS Biol. 9, e1001083
35. Su, Y., Ospina, J. K., Zhang, J., Michelson, A. P., Schoen, A. M., and Zhu, A. J. (2011) Sequential phosphorylation of smoothened transduces graded hedgehog signaling Sci. Signaling 4, ra43
36. Nigg, E. A. and Raff, J. W. (2009) Centrioles, centrosomes, and cilia in health and disease Cell 139, 663-678
37. Willert, K., Brown, J. D., Danenberg, E., Duncan, A. W., Weissman, I. L., Reya, T., Yates, J. R., 3rd, and Nusse, R. (2003) Wnt proteins are lipid-modified and can act as stem cell growth factors Nature 423, 448-452 (Pubitemid 36626997)
38. Nybakken, K., Vokes, S. A., Lin, T. Y., McMahon, A. P., and Perrimon, N. (2005) A genome-wide RNA interference screen in Drosophila melanogaster cells for new components of the Hh signaling pathway Nat. Genet. 37, 1323-1332 (Pubitemid 41722187)
39. Corbit, K. C., Shyer, A. E., Dowdle, W. E., Gaulden, J., Singla, V., and Reiter, J. F. (2008) Kif3a constrains beta-catenin-dependent Wnt signalling through dual ciliary and non-ciliary mechanisms Nat. Cell Biol. 10, 70-76
40. Chan, J. A., Balasubramanian, S., Witt, R. M., Nazemi, K. J., Choi, Y., Pazyra-Murphy, M. F., Walsh, C. O., Thompson, M., and Segal, R. A. (2009) Proteoglycan interactions with Sonic Hedgehog specify mitogenic responses Nat. Neurosci. 12, 409-417