Histone deacetylase 6 represents a novel drug target in the oncogenic Hedgehog signaling pathway

Molecular Cancer Therapeutics

Volumn 14, Issue 3, 2015, Pages 727-739

  Dhanyamraju, Pavan Kumar ^a   Holz, Philipp Simon ^a   Finkernagel, Florian ^a   Fendrich, Volker ^a   Lauth, Matthias ^a  

^a PHILIPPS UNIVERSITY MARBURG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

CASPASE 3; CAY 10603; HISTONE DEACETYLASE 6; HISTONE DEACETYLASE INHIBITOR; MESSENGER RNA; PROTEIN PATCHED 1; RICOLINOSTAT; SMOOTHENED PROTEIN; SONIC HEDGEHOG PROTEIN; TRANSCRIPTION FACTOR GLI2; TRANSCRIPTION FACTOR GLI3; TUBACIN; UNCLASSIFIED DRUG; VISMODEGIB; CELL SURFACE RECEPTOR; GLI3 PROTEIN, MOUSE; HDAC6 PROTEIN, MOUSE; HISTONE DEACETYLASE; KRUPPEL LIKE FACTOR; NERVE PROTEIN; PATCHED RECEPTORS;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CANCER INHIBITION; CARCINOGENESIS; COMPARATIVE STUDY; CONTROLLED STUDY; CYTOTOXICITY; ENZYME ACTIVITY; ENZYME ANALYSIS; ENZYME INHIBITION; GENE EXPRESSION; GENETIC TRANSCRIPTION; HUMAN; HUMAN CELL; IN VIVO STUDY; MEDULLOBLASTOMA; MOLECULARLY TARGETED THERAPY; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; 3T3 CELL LINE; ANIMAL; C57BL MOUSE; CELL LINE; CELL SURVIVAL; CEREBELLUM TUMOR; GENE EXPRESSION PROFILING; GENETICS; PROCEDURES; TUMOR CELL LINE;

ANIMALS; CELL LINE; CELL LINE, TUMOR; CELL SURVIVAL; CEREBELLAR NEOPLASMS; GENE EXPRESSION; GENE EXPRESSION PROFILING; HEDGEHOG PROTEINS; HISTONE DEACETYLASES; KRUPPEL-LIKE TRANSCRIPTION FACTORS; MEDULLOBLASTOMA; MICE; MICE, INBRED C57BL; NERVE TISSUE PROTEINS; NIH 3T3 CELLS; RECEPTORS, CELL SURFACE; SIGNAL TRANSDUCTION;

EID: 84929612574     PISSN: 15357163     EISSN: 15388514     Source Type: Journal    
DOI: 10.1158/1535-7163.MCT-14-0481     Document Type: Article

References (80)

1. Bourdeaut F, Miquel C, Alapetite C, Roujeau T, Doz F. Medulloblas-tomas: update on a heterogeneous disease. Curr Opin Oncol 2011;23: 630-7.
2. Northcott PA, Jones DT, Kool M, Robinson GW, Gilbertson RJ, Cho YJ, et al. Medulloblastomics: the end of the beginning. Nat Rev Cancer 2012;12: 818-34.
3. Kool M, Jones DT, Jager N, Northcott PA, Pugh TJ, Hovestadt V, et al. Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition. Cancer Cell 2014;25: 393-405.
4. Rohatgi R, Milenkovic L, Scott MP. Patched1 regulates hedgehog signaling at the primary cilium. Science 2007;317:372-6.
5. Nozawa YI, Lin C, Chuang PT. Hedgehog signalingfrom the primary cilium to the nucleus: an emerging picture of ciliary localization, trafficking and transduction. Curr Opin Genet Dev 2013;23:429-37.
6. Kim S, Dynlacht BD. Assembling a primary cilium. Current opinion in cell biology 2013;25:506-11.
7. LiemKFJr, Ashe A, He M, Satir P, Moran J, Beier D, et al. The IFT-A complex regulates Shh signaling through cilia structure and membrane protein trafficking. J Cell Biol 2012;197:789-800.
8. Hubbert C, Guardiola A, Shao R, Kawaguchi Y, Ito A, Nixon A, et al. HDAC6 is a microtubule-associated deacetylase. Nature 2002;417:455-8.
9. Pugacheva EN, Jablonski SA, Hartman TR, Henske EP, Golemis EA. HEF1-dependent Aurora A activation induces disassembly of the primary cilium. Cell 2007;129:1351-63.
10. Tukachinsky H, Lopez LV, Salic A. A mechanism for vertebrate Hedgehog signaling: recruitment to cilia and dissociation of SuFu-Gli protein complexes. J Cell Biol 2010;191:415-28.
11. Wen X, Lai CK, Evangelista M, Hongo JA, de Sauvage FJ, Scales SJ. Kinetics of hedgehog-dependent full-length Gli3 accumulation in primary cilia and subsequent degradation. Mol Cell Biol 2010;30:1910-22.
12. Kim J, Kato M, Beachy PA. Gli2 trafficking links Hedgehog-dependent activation of Smoothened in the primary cilium to transcriptional activation in the nucleus. Proc Natl Acad Sci U S A 2009;106:21666-71.
13. Low JA, de Sauvage FJ. Clinical experience with Hedgehog pathway inhibitors. J Clin Oncol 2010;28:5321-6.
14. Metcalfe C, de Sauvage FJ. Hedgehog fights back: mechanisms of acquired resistance against Smoothened antagonists. Cancer Res 2011;71:5057-61.
15. Rudin CM, Hann CL, Laterra J, Yauch RL, Callahan CA, Fu L, et al.Treatment of medulloblastoma with hedgehog pathway inhibitor GDC-0449. N Engl J Med 2009;361:1173-8.
16. Von Hoff DD, LoRusso PM, Rudin CM, Reddy JC, Yauch RL, Tibes R, et al. Inhibition of the hedgehog pathway in advanced basal-cell carcinoma. N Engl J Med 2009;361:1164-72.
17. Yauch RL, Dijkgraaf GJ, Alicke B, Januario T, Ahn CP, Holcomb T, et al. Smoothened mutation confers resistancetoaHedgehogpathway inhibitor in medulloblastoma. Science 2009;326:572-4.
18. Buonamici S, Williams J, Morrissey M, Wang A, Guo R, Vattay A, et al. Interfering with resistance to smoothened antagonists by inhibition of the PI3K pathway in medulloblastoma. Sci Transl Med 2010;2:51ra70.
19. Zhang Y, Kwon S, Yamaguchi T, Cubizolles F, Rousseaux S, Kneissel M, et al. Mice lacking histone deacetylase 6 have hyperacetylated tubulin but are viable and develop normally. Mol Cell Biol 2008;28:1688-701.
20. Svard J, Heby-Henricson K, Persson-Lek M, Rozell B, Lauth M, Bergstrom A, et al. Genetic elimination of Suppressor of fused reveals an essential repressor function in the mammalian Hedgehog signaling pathway. Dev Cell 2006;10:187-97.
21. Lipinski RJ, Bijlsma MF, Gipp JJ, Podhaizer DJ, Bushman W.Establishment and characterizationofimmortalized Gli-nullmouse embryonicfibroblast cell lines. BMC Cell Biol 2008;9:49.
22. Hallahan AR, Pritchard JI, Hansen S, Benson M, Stoeck J, Hatton BA, et al. The SmoA1 mouse model reveals that notch signaling is critical for the growth and survival of sonic hedgehog-induced medulloblastomas. Cancer Res 2004;64:7794-800.
23. Adhikary T, Kaddatz K, Finkernagel F, Schonbauer A, Meissner W, Scharfe M, et al. Genomewide analyses define different modes of transcriptional regulation by peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta). PLoS ONE 2011;6:e16344.
24. Aldana-Masangkay GI, Sakamoto KM. The role of HDAC6 in cancer. J Biomed Biotechnol 2010;2011:875824.
25. Lee YS, Lim KH, Guo X, Kawaguchi Y, Gao Y, Barrientos T, et al. The cytoplasmic deacetylase HDAC6 is required for efficient oncogenic tumor-igenesis. Cancer Res 2008;68:7561-9.
26. Santo L, Hideshima T, Kung AL, Tseng JC, Tamang D, Yang M, et al. Preclinical activity, pharmacodynamic, and pharmacokinetic properties of a selective HDAC6 inhibitor, ACY-1215, in combination with bortezomib in multiple myeloma. Blood 2012;119:2579-89.
27. Jacob LS, Wu X, Dodge ME, Fan CW, Kulak O, Chen B, et al. Genome-wide RNAi screen reveals disease-associated genes that are common to Hedgehog and Wnt signaling. Sci Signal 2011;4:ra4.
28. Lee SJ, Lindsey S, Graves B, Yoo S, Olson JM, Langhans SA. Sonic hedgehog-induced histone deacetylase activation is required for cerebellar granule precursor hyperplasia in medulloblastoma. PLoS ONE 2013;8:e71455.
29. Hatton BA, Villavicencio EH, Tsuchiya KD, Pritchard JI, Ditzler S, Pullar B, et al. The Smo/Smo model: hedgehog-induced medulloblastoma with 90% incidence and leptomeningeal spread. Cancer Res 2008;68:1768-76.
30. Haggarty SJ, Koeller KM, Wong JC, Grozinger CM, Schreiber SL. Domain-selective small-molecule inhibitor of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation. Proc Natl Acad Sci U S A 2003;100: 4389-94.
31. Kozikowski AP, Tapadar S, Luchini DN, Kim KH, Billadeau DD. Use of the nitrile oxide cycloaddition (NOC) reaction for molecular probe generation: a new class of enzyme selective histone deacetylase inhibitors (HDACIs) showing picomolar activity at HDAC6. J Med Chem 2008;51:4370-3.
32. Chen JK, Taipale J, Young KE, Maiti T, Beachy PA. Small molecule modulation of Smoothened activity. Proc Natl Acad Sci U S A 2002;99: 14071-6.
33. Cooper AF, Yu KP, Brueckner M, Brailey LL, Johnson L, McGrath JM, et al. Cardiac and CNS defects ina mouse with targeted disruption of suppressor of fused. Development 2005;132:4407-17.
34. Canettieri G, DiMarcotullio L, Greco A, Coni S, Antonucci L, Infante P, et al. Histone deacetylase and Cullin3-REN(KCTD11) ubiquitin ligase interplay regulates Hedgehog signalling through Gli acetylation. Nat Cell Biol 2010;12:132-42.
35. Boyault C, Zhang Y, Fritah S, Caron C, Gilquin B, Kwon SH, et al. HDAC6 controls major cell response pathways tocytotoxicaccumulation ofprotein aggregates. Genes Dev 2007;21:2172-81.
36. Bazzaro M, Lin Z, Santillan A, Lee MK, Wang MC, Chan KC, et al. Ubiquitin proteasome system stress underlies synergistic killing of ovarian cancer cells by bortezomib and a novel HDAC6 inhibitor. Clin Cancer Res 2008;14:7340-7.
37. Boyault C, Gilquin B, Zhang Y, Rybin V, Garman E, Meyer-Klaucke W, et al. HDAC6-p97/VCP controlled polyubiquitin chain turnover. Embo J 2006; 25:3357-66.
38. Hebron ML, Lonskaya I, Sharpe K, Weerasinghe PP, Algarzae NK, Shekoyan AR, et al. Parkin ubiquitinates Tar-DNA binding protein-43 (TDP-43) and promotes its cytosolic accumulation via interaction with histone deacety-lase 6 (HDAC6). J Biol Chem 2013;288:4103-15.
39. Lee JY, Koga H, Kawaguchi Y, Tang W, Wong E, Gao YS, et al. HDAC6 controls autophagosome maturation essential for ubiquitin-selective quality-control autophagy. Embo J 2010;29:969-80.
40. Pandey UB, Batlevi Y, Baehrecke EH, Taylor JP. HDAC6 at the intersection of autophagy, the ubiquitin-proteasome system and neurodegeneration. Autophagy 2007;3:643-5.
41. Pandey UB, Nie Z, Batlevi Y, McCray BA, Ritson GP, Nedelsky NB, et al. HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS. Nature 2007;447:859-63.
42. Chen PB, Hung JH, Hickman TL, Coles AH, Carey JF, Weng Z, et al. Hdac6 regulates Tip60-p400 function in stem cells. Elife 2013;2:e01557.
43. Kovacs JJ, Murphy PJ, Gaillard S, Zhao X, Wu JT, Nicchitta CV, et al. HDAC6 regulates Hsp90 acetylation and chaperone-dependent activation of glu-cocorticoid receptor. Mol Cell 2005;18:601-7.
44. Matthias P, Yoshida M, Khochbin S. HDAC6 a new cellular stress surveillance factor. Cell Cycle 2008;7:7-10.
45. Valenzuela-Fernandez A, Cabrero JR, Serrador JM, Sanchez-Madrid F. HDAC6: a key regulator of cytoskeleton, cell migration and cell-cell interactions. Trends Cell Biol 2008;18:291-7.
46. Parmigiani RB, Xu WS, Venta-Perez G, Erdjument-Bromage H, Yaneva M, Tempst P, et al. HDAC6 is a specific deacetylase of peroxiredoxins and is involved in redox regulation. Proc Natl Acad Sci U S A 2008;105:9633-8.
47. Zhang X, Yuan Z, Zhang Y, Yong S, Salas-Burgos A, Koomen J, et al. HDAC6 modulates cell motility by altering the acetylation level of cortactin. Mol Cell 2007;27:197-213.
48. Wilson-Edell KA, Kehasse A, Scott GK, Yau C, Rothschild DE, Schilling B, et al. RPL24: a potential therapeutic target whose depletion or acetylation inhibits polysome assembly and cancer cell growth. Oncotarget 2014;5: 5165-76.
49. Kamemura K, Ogawa M, Ohkubo S, Ohtsuka Y, Shitara Y, Komiya T, et al. Depression of mitochondrial metabolism by downregulation of cyto-plasmic deacetylase, HDAC6. FEBS Lett 2012;586:1379-83.
50. Zhang Y, Li N, Caron C, Matthias G, Hess D, Khochbin S, et al. HDAC-6 interacts with and deacetylates tubulin and microtubules in vivo. Embo J 2003;22:1168-79.
51. Dompierre JP, Godin JD, Charrin BC, Cordelieres FP, King SJ, Humbert S, et al. Histone deacetylase 6 inhibition compensates for the transport deficit in Huntington's disease by increasing tubulin acetylation. J Neurosci 2007;27:3571-83.
52. Zilberman Y, Ballestrem C, Carramusa L, Mazitschek R, Khochbin S, Bershadsky A. Regulation of microtubule dynamics by inhibition of the tubulin deacetylase HDAC6. J Cell Sci 2009;122:3531-41.
53. Chen S, Owens GC, Makarenkova H, Edelman DB. HDAC6 regulates mitochondrial transport in hippocampal neurons. PLoS ONE 2010;5: e10848.
54. Kwon S, Zhang Y, Matthias P. The deacetylase HDAC6 is a novel critical component of stress granules involved in the stress response. Genes Dev 2007;21:3381-94.
55. Kawaguchi Y, Kovacs JJ, McLaurin A, Vance JM, Ito A, Yao TP. The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress. Cell 2003;115:727-38.
56. Deribe YL, Wild P, Chandrashaker A, Curak J, Schmidt MH, Kalaidzidis Y, et al. Regulation of epidermal growth factor receptor trafficking by lysine deacetylase HDAC6. Sci Signal 2009;2:ra84.
57. Spange S, Wagner T, Heinzel T, Kramer OH. Acetylation of non-histone proteins modulates cellular signalling at multiple levels. Int J Biochem Cell Biol 2009;41:185-98.
58. Yang MH, Laurent G, Bause AS, Spang R, German N, Haigis MC, et al. HDAC6 and SIRT2 regulate the acetylation state and oncogenic activity of mutant K-RAS. Mol Cancer Res 2013;11:1072-7.
59. Shan B, Yao TP, Nguyen HT, Zhuo Y, Levy DR, Klingsberg RC, et al. Requirement of HDAC6 for transforming growth factor-beta1-induced epithelial-mesenchymal transition. J Biol Chem 2008;283: 21065-73.
60. Palijan A, Fernandes I, Bastien Y, Tang L, Verway M, Kourelis M, et al. Function of histone deacetylase 6 as a cofactor of nuclear receptor cor-egulator LCoR. J Biol Chem 2009;284:30264-74.
61. Ozaki T, Wu D, Sugimoto H, Nagase H, Nakagawara A. Runt-related transcription factor 2(RUNX2) inhibits p53-dependent apoptosis through the collaboration withHDAC6inresponsetoDNA damage. Cell Death Dis 2013;4:e610.
62. Westendorf JJ, Zaidi SK, Cascino JE, Kahler R, van Wijnen AJ, Lian JB, et al. Runx2 (Cbfa1, AML-3) interacts with histone deacetylase 6 and represses the p21(CIP1/WAF1) promoter. Mol Cell Biol 2002;22:7982-92.
63. Jochems J, Boulden J, Lee BG, Blendy JA, Jarpe M, Mazitschek R, et al. Antidepressant-like properties of novel HDAC6-selective inhibitors with improved brain bioavailability. Neuropsychopharmacology 2014; 39:389-400.
64. Lauth M, Rohnalter V, Bergstrom A, Kooshesh M, Svenningsson P, Toftgard R. Antipsychotic drugs regulate hedgehog signaling by modulation of 7-dehydrocholesterol reductase levels. Mol Pharmacol 2010; 78:486-96.
65. Bijlsma MF, Damhofer H, Roelink H. Hedgehog-stimulated chemotaxis is mediated by smoothened located outside the primary cilium. Sci Signal 2012;5:ra60.
66. Chinchilla P, Xiao L, Kazanietz MG, Riobo NA. Hedgehog proteins activate pro-angiogenic responses in endothelial cells through non-canonical signaling pathways. Cell Cycle 2010;9:570-79.
67. Dorn KV, Hughes CE, Rohatgi R. A Smoothened-Evc2 complex transduces the Hedgehog signal at primary cilia. Dev Cell 2012;23:823-35.
68. Corbit KC, Aanstad P, Singla V, Norman AR, Stainier DY, Reiter JF. Vertebrate Smoothened functions at the primary cilium. Nature 2005;437: 1018-21.
69. Huangfu D, Liu A, Rakeman AS, Murcia NS, Niswander L, Anderson KV. Hedgehog signalling in the mouse requires intraflagellar transport proteins. Nature 2003;426:83-7.
70. Han YG, Kim HJ, Dlugosz AA, Ellison DW, Gilbertson RJ, Alvarez-Buylla A. Dual and opposing roles of primary cilia in medulloblastoma development. Nat Med 2009;15:1062-5.
71. Cervantes S, Lau J, Cano DA, Borromeo-Austin C, Hebrok M. Primary cilia regulate Gli/hedgehog activation in pancreas. Proc Natl Acad Sci U S A 2010;107:10109-14.
72. Ho L, Ali SA, Al-Jazrawe M, Kandel R, Wunder JS, Alman BA. Primary cilia attenuate hedgehog signalling in neoplastic chondrocytes. Oncogene 2013;32:5388-96.
73. Haycraft CJ, Banizs B, Aydin-Son Y, Zhang Q, Michaud EJ, Yoder BK. Gli2 and Gli3 localize to cilia and require the intraflagellar transport protein polaris for processing and function. PLoS Genet 2005;1:e53.
74. Wong SY, Seol AD, So PL, Ermilov AN, Bichakjian CK, Epstein EH Jr, et al. Primary cilia can both mediate and suppress Hedgehog pathway-dependent tumorigenesis. Nat Med 2009;15:1055-61.
75. Jia J, Kolterud A, Zeng H, Hoover A, Teglund S, Toftgard R, et al. Suppressor of Fused inhibits mammalian Hedgehog signaling in the absence of cilia. Dev Biol 2009;330:452-60.
76. Chen MH, Wilson CW, Li YJ, Law KK, Lu CS, Gacayan R, et al. Cilium-independent regulation of Gli protein function by Sufu in Hedgehog signaling is evolutionarily conserved. Genes Dev 2009;23:1910-28.
77. de la Roche M, Ritter AT, Angus KL, Dinsmore C, Earnshaw CH, Reiter JF, et al. Hedgehog signaling controls T cell killing at the immunological synapse. Science 2013;342:1247-50.
78. Serrador JM, Cabrero JR, Sancho D, Mittelbrunn M, Urzainqui A, Sanchez-Madrid F. HDAC6 deacetylase activity links the tubulin cytoskeleton with immune synapse organization. Immunity 2004;20:417-28.
79. Aldana-Masangkay GI, Rodriguez-Gonzalez A, Lin T, Ikeda AK, Hsieh YT, Kim YM, et al. Tubacin suppresses proliferation and induces apoptosis of acute lymphoblastic leukemia cells. Leuk Lymphoma 2011;52:1544-55.
80. Gradilone SA, Radtke BN, Bogert PS, Huang BQ, Gajdos GB, LaRusso NF. HDAC6 inhibition restores ciliary expression and decreases tumor growth. Cancer Res 2013;73:2259-70.