The Hedgehog processing pathway is required for NSCLC growth and survival

Oncogene

Volumn 32, Issue 18, 2013, Pages 2335-2345

  Rodriguez Blanco, J ^a   Schilling, N S ^a,b   Tokhunts, R ^a,b   Giambelli, C ^a   Long, J ^a   Liang Fei, D ^a,b   Singh, S ^a   Black, K E ^a   Wang, Z ^a   Galimberti, F ^b   Bejarano, P A ^a   Elliot, S ^a   Glassberg, M K ^c   Nguyen, D M ^a,d   Lockwood, W W ^e   Lam, W L ^f   Dmitrovsky, E ^b,g   Capobianco, A J ^a,d   Robbins, D J ^a,d  

^a UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE   (United States)

^b DARTMOUTH MEDICAL SCHOOL   (United States)

^c UNIVERSITY OF MIAMI   (United States)

^d UNIVERSITY OF MIAMI   (United States)

^e NATIONAL HUMAN GENOME RESEARCH INSTITUTE   (United States)

^f BRITISH COLUMBIA CANCER RESEARCH CENTRE   (Canada)

^g DARTMOUTH HITCHCOCK MEDICAL CENTER   (United States)

Author keywords

dispatched; hedgehog; hedgehog acyltransferase; lung cancer; skinny hedgehog

Indexed keywords

ACYLTRANSFERASE; MEMBRANE PROTEIN; PROTEIN DISP 1; PROTEIN SKN; SMOOTHENED PROTEIN; SONIC HEDGEHOG PROTEIN; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; APOPTOSIS; ARTICLE; CANCER CELL; CANCER GROWTH; CANCER SURVIVAL; CELL PROLIFERATION; CONTROLLED STUDY; ENZYME ACTIVITY; HUMAN; HUMAN CELL; HUMAN TISSUE; LUNG NON SMALL CELL CANCER; MITOSIS; MOUSE; NONHUMAN; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PROCESSING; SIGNAL TRANSDUCTION; TUMOR VOLUME;

ACYLTRANSFERASES; AMINO ACID SEQUENCE; ANIMALS; CARCINOMA, NON-SMALL-CELL LUNG; CELL LINE, TUMOR; CELL SURVIVAL; HEDGEHOG PROTEINS; HUMANS; LUNG NEOPLASMS; MEMBRANE PROTEINS; MICE; MICE, TRANSGENIC; MOLECULAR SEQUENCE DATA; RABBITS; RECEPTORS, G-PROTEIN-COUPLED; SIGNAL TRANSDUCTION; XENOGRAFT MODEL ANTITUMOR ASSAYS;

ERINACEIDAE;

EID: 84877583655     PISSN: 09509232     EISSN: 14765594     Source Type: Journal    
DOI: 10.1038/onc.2012.243     Document Type: Article

References (79)

1. Ingham PW, McMahon AP. Hedgehog signaling in animal development: paradigms and principles. Genes Dev 2001; 15: 3059-3087.
2. Farzan SF, Singh S, Schilling NS, Robbins DJ. The adventures of sonic hedgehog in development and repair. III. Hedgehog processing and biological activity. Am J Physiol Gastrointest Liver Physiol 2008; 294: G844-G849.
3. Teglund S, Toftgd R. Hedgehog beyond medulloblastoma and basal cell carcinoma. Biochim Biophys Acta 2010; 1805: 181-208.
4. Yang L, Xie G, Fan Q, Xie J. Activation of the hedgehog-signaling pathway in human cancer and the clinical implications. Oncogene 2010; 29: 469-481.
5. Stone DM, Hynes M, Armanini M, Swanson TA, Gu Q, Johnson RL et al. The tumour-suppressor gene patched encodes a candidate receptor for Sonic hedgehog. Nature 1996; 384: 129-134.
6. Marigo V, Davey RA, Zuo Y, Cunningham JM, Tabin CJ. Biochemical evidence that patched is the Hedgehog receptor. Nature 1996; 384: 176-179.
7. Chen Y, Struhl G. Dual roles for patched in sequestering and transducing Hedgehog. Cell 1996; 87: 553-563.
8. Quirk J, van den Heuvel M, Henrique D, Marigo V, Jones TA, Tabin C et al. The smoothened gene and hedgehog signal transduction in Drosophila and vertebrate development. Cold Spring Harb Symp Quant Biol 1997; 62: 217-226.
9. Stecca B, Ruiz i Altaba A. Context-dependent regulation of the GLI code in cancer by HEDGEHOG and non-HEDGEHOG signals. J Mol Cell Biol 2010; 2: 84-95.
10. Hoff Von 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: 1164-1172.
11. 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: 1173-1178.
12. Low JA, de Sauvage FJ. Clinical experience with Hedgehog pathway inhibitors. J Clin Oncol 2010; 28: 5321-5326.
13. Yauch RL, Dijkgraaf GJP, Alicke B, Januario T, Ahn CP, Holcomb T et al. Smoothened mutation confers resistance to a Hedgehog pathway inhibitor in medulloblastoma. Science 2009; 326: 572-574.
14. Dijkgraaf GJP, Alicke B, Weinmann L, Januario T, West K, Modrusan Z et al. Small molecule inhibition of GDC-0449 refractory smoothened mutants and downstream mechanisms of drug resistance. Cancer Res 2011; 71: 435-444.
15. Mann RK, Beachy PA. Novel lipid modifications of secreted protein signals. Annu Rev Biochem 2004; 73: 891-923.
16. Porter JA, Young KE, Beachy PA. Cholesterol modification of hedgehog signaling proteins in animal development. Science 1996; 274: 255-259.
17. Pepinsky RB, Zeng C, Wen D, Rayhorn P, Baker DP, Williams KP et al. Identification of a palmitic acid-modified form of human Sonic hedgehog. J Biol Chem 1998; 273: 14037-14045.
18. Chamoun Z, Mann RK, Nellen D, Kessler von DP, Bellotto M, Beachy PA et al. Skinny hedgehog, an acyltransferase required for palmitoylation and activity of the hedgehog signal. Science 2001; 293: 2080-2084.
19. Lee JD, Treisman JE. Sightless has homology to transmembrane acyltransferases and is required to generate active Hedgehog protein. Curr Biol 2001; 11: 1147-1152.
20. Amanai K, Jiang J. Distinct roles of Central missing and Dispatched in sending the Hedgehog signal. Development 2001; 128: 5119-5127.
21. Micchelli CA, The I, Selva E, Mogila V, Perrimon N. Rasp, a putative transmembrane acyltransferase, is required for Hedgehog signaling. Development 2001; 129: 843-851.
22. Buglino JA, Resh MD. Hhat is a palmitoylacyltransferase with specificity for N-palmitoylation of Sonic Hedgehog. J Biol Chem 2008; 283: 22076-22088.
23. Taylor FR, Wen D, Garber EA, Carmillo AN, Baker DP, Arduini RM et al. Enhanced potency of human Sonic hedgehog by hydrophobic modification. Biochemistry 2001; 40: 4359-4371.
24. Kohtz JD, Lee HY, Gaiano N, Segal J, Ng E, Larson T et al. N-terminal fatty-acylation of sonic hedgehog enhances the induction of rodent ventral forebrain neurons. Development 2001; 128: 2351-2363.
25. Burke R, Nellen D, Bellotto M, Hafen E, Senti KA, Dickson BJ et al. Dispatched, a novel sterol-sensing domain protein dedicated to the release of cholesterolmodified hedgehog from signaling cells. Cell 1999; 99: 803-815.
26. Caspary T, Garca-Garca MJ, Huangfu D, Eggenschwiler JT, Wyler MR, Rakeman AS et al. Mouse Dispatched homolog1 is required for long-range, but not juxtacrine, Hh signaling. Curr Biol 2002; 12: 1628-1632.
27. Ma Y, Erkner A, Gong R, Yao S, Taipale J, Basler K et al. Hedgehog-mediated patterning of the mammalian embryo requires transporter-like function of dispatched. Cell 2002; 111: 63-75.
28. Kawakami T, Kawcak T, Li Y-J, Zhang W, Hu Y, Chuang P-T. Mouse dispatched mutants fail to distribute hedgehog proteins and are defective in hedgehog signaling. Development 2002; 129: 5753-5765.
29. Chen MH, Li YJ, Kawakami T, Xu SM, Chuang PT. Palmitoylation is required for the production of a soluble multimeric Hedgehog protein complex and long-range signaling in vertebrates. Genes Dev 2004; 18: 641-659.
30. Zhang XM, Ramalho-Santos M, McMahon AP. Smoothened mutants reveal redundant roles for Shh and Ihh signaling including regulation of L/R asymmetry by the mouse node. Cell 2001; 105: 781-792.
31. Singh S, Wang Z, Liang Fei D, Black KE, Goetz JA, Tokhunts R et al. Hedgehog-Producing Cancer Cells Respond to and Require Autocrine Hedgehog Activity. Cancer Res 2011; 71: 4454-4463.
32. Yuan Z, Goetz JA, Singh S, Ogden SK, Petty WJ, Black CC et al. Frequent requirement of hedgehog signaling in non-small cell lung carcinoma. Oncogene 2007; 26: 1046-1055.
33. Ma Y, Fiering S, Black C, Liu X, Yuan Z, Memoli VA et al. Transgenic cyclin E triggers dysplasia and multiple pulmonary adenocarcinomas. Proc Natl Acad Sci USA 2007; 104: 4089-4094.
34. Gialmanidis IP, Bravou V, Amanetopoulou SG, Varakis J, Kourea H, Papadaki H. Overexpression of hedgehog pathway molecules and FOXM1 in non-small cell lung carcinomas. Lung Cancer 2009; 66: 64-74.
35. Chen JK, Taipale J, Young KE, Maiti T, Beachy PA. Small molecule modulation of Smoothened activity. Proc Natl Acad Sci USA 2002; 99: 14071-14076.
36. Cooper MK, Porter JA, Young KE, Beachy PA. Teratogen-mediated inhibition of target tissue response to Shh signaling. Science 1998; 280: 1603-1607.
37. Liu X, Sempere LF, Galimberti F, Freemantle SJ, Black C, Dragnev KH et al. Uncovering growth-suppressive MicroRNAs in lung cancer. Clin Cancer Res 2009; 15: 1177-1183.
38. Legrand C, Bour JM, Jacob C, Capiaumont J, Martial A, Marc A et al. Lactate dehydrogenase (LDH) activity of the cultured eukaryotic cells as marker of the number of dead cells in the medium [corrected]. J Biotechnol 1992; 25: 231-243.
39. Fei DL, Li H, Kozul CD, Black KE, Singh S, Gosse JA et al. Activation of Hedgehog signaling by the environmental toxicant arsenic may contribute to the etiology of arsenic-induced tumors. Cancer Res 2010; 70: 1981-1988.
40. Katoh Y, Katoh M. Hedgehog target genes: mechanisms of carcinogenesis induced by aberrant hedgehog signaling activation. Curr Mol Med 2009; 9: 873-886.
41. Miura GI, Buglino J, Alvarado D, Lemmon MA, Resh MD, Treisman JE. Palmitoylation of the EGFR ligand Spitz by Rasp increases Spitz activity by restricting its diffusion. Dev Cell 2006; 10: 167-176.
42. Sinha S, Chen JK. Purmorphamine activates the Hedgehog pathway by targeting Smoothened. Nat Chem Biol 2006; 2: 29-30.
43. Lockwood WW, Chari R, Coe BP, Thu KL, Garnis C, Malloff CA et al. Integrative genomic analyses identify BRF2 as a novel lineage-specific oncogene in lung squamous cell carcinoma. Plos Med 2010; 7.
44. Neal JW, Sequist LV. Exciting new targets in lung cancer therapy: ALK, IGF-1R, HDAC, and Hh. Curr Treat Options Oncol 2010; 11: 36-44.
45. Lauth M, Bergstrom A, Shimokawa T, Toftgd R. Inhibition of GLI-mediated transcription and tumor cell growth by small-molecule antagonists. Proc Natl Acad Sci USA 2001; 104: 8455-8460.
46. Ng JMY, Curran T. The Hedgehog's tale: developing strategies for targeting cancer. Nat Rev Cancer 2011; 11: 493-501.
47. Petersen I, Bujard M, Petersen S, Wolf G, Goeze A, Schwendel A et al. Patterns of chromosomal imbalances in adenocarcinoma and squamous cell carcinoma of the lung. Cancer Res 1997; 57: 2331-2335.
48. Tai ALS, Yan W-S, Fang Y, Xie D, Sham JST, Guan X-Y. Recurrent chromosomal imbalances in nonsmall cell lung carcinoma: the association between 1q amplification and tumor recurrence. Cancer 2004; 100: 1918-1927.
49. Johnson RL, Rothman AL, Xie J, Goodrich LV, Bare JW, Bonifas JM et al. Human homolog of patched, a candidate gene for the basal cell nevus syndrome. Science 1996; 272: 1668-1671.
50. Hahn H, Wicking C, Zaphiropoulous PG, Gailani MR, Shanley S, Chidambaram A et al. Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome. Cell 1996; 85: 841-851.
51. Xie J, Johnson RL, Zhang X, Bare JW, Waldman FM, Cogen PH et al. Mutations of the PATCHED gene in several types of sporadic extracutaneous tumors. Cancer Res 1997; 57: 2369-2372.
52. Goodrich LV, Milenkovic L, Higgins KM, Scott MP. Altered neural cell fates and medulloblastoma in mouse patched mutants. Science 1997; 277: 1109-1113.
53. Adolphe C, Hetherington R, Ellis T, Wainwright B. Patched1 functions as a gatekeeper by promoting cell cycle progression. Cancer Res 2006; 66: 2081-2088.
54. Tostar U, Malm CJ, Meis-Kindblom JM, Kindblom L-G, Toftgd R, Unden AB. Deregulation of the hedgehog signalling pathway: a possible role for the PTCH and SUFU genes in human rhabdomyoma and rhabdomyosarcoma development. J Pathol 2006; 208: 17-25.
55. Shen T, Park WS, Bo ni R, Saini N, Pham T, Lash AE et al. Detection of loss of heterozygosity on chromosome 9q22.3 in microdissected sporadic basal cell carcinoma. Hum Pathol 1999; 30: 284-287.
56. Xie J, Murone M, Luoh SM, Ryan A, Gu Q, Zhang C et al. Activating Smoothened mutations in sporadic basal-cell carcinoma. Nature 1998; 391: 90-92.
57. Kubo M, Nakamura M, Tasaki A, Yamanaka N, Nakashima H, Nomura M et al. Hedgehog signaling pathway is a new therapeutic target for patients with breast cancer. Cancer Res 2004; 64: 6071-6074.
58. Thayer SP, di Magliano MP, Heiser PW, Nielsen CM, Roberts DJ, Lauwers GY et al. Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis. Nature 2003; 425: 851-856.
59. Berman DM, Karhadkar SS, Maitra A, Montes De Oca R, Gerstenblith MR, Briggs K et al. Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours. Nature 2003; 425: 846-851.
60. Watkins DN, Berman DM, Burkholder SG, Wang B, Beachy PA, Baylin SB. Hedgehog signalling within airway epithelial progenitors and in small-cell lung cancer. Nature 2003; 422: 313-317.
61. Clement V, Sanchez P, de Tribolet N, Radovanovic I, Ruiz i Altaba A. HEDGEHOGGLI1 signaling regulates human glioma growth, cancer stem cell self-renewal, and tumorigenicity. Curr Biol 2007; 17: 165-172.
62. Karhadkar SS, Bova GS, Abdallah N, Dhara S, Gardner D, Maitra A et al. Hedgehog signalling in prostate regeneration, neoplasia and metastasis. Nature 2004; 431: 707-712.
63. Sanchez P, Hernandez AM, Stecca B, Kahler AJ, DeGueme AM, Barrett A et al. Inhibition of prostate cancer proliferation by interference with SONIC HEDGEHOG-GLI1 signaling. Proc Natl Acad Sci USA 2004; 101: 12561-12566.
64. Mas C. Ruiz i Altaba A. Small molecule modulation of HH-GLI signaling: current leads, trials and tribulations. Biochem Pharmacol 2010; 80: 712-723.
65. Stanton BZ, Peng LF. Small-molecule modulators of the Sonic Hedgehog signaling pathway. Mol Biosyst 2010; 6: 44-54.
66. Yauch RL, Gould SE, Scales SJ, Tang T, Tian H, Ahn CP et al. A paracrine requirement for hedgehog signalling in cancer. Nature 2008; 455: 406-410.
67. Lauth M, Bergstrom A, Shimokawa T, Tostar U, Jin Q, Fendrich V et al. DYRK1Bdependent autocrine-to-paracrine shift of Hedgehog signaling by mutant RAS. Nat Struct Mol Biol 2010; 17: 718-725.
68. Park K-S, Martelotto LG, Peifer M, Sos ML, Karnezis AN, Mahjoub MR et al. A crucial requirement for Hedgehog signaling in small cell lung cancer. Nat Med 2011; 17: 1504-1508.
69. Singh S, Tokhunts R, Baubet V, Goetz JA, Huang ZJ, Schilling NS et al. Sonic hedgehog mutations identified in holoprosencephaly patients can act in a dominant negative manner. Hum Genet 2009; 125: 95-103.
70. Moffat J, Grueneberg DA, Yang X, Kim SY, Kloepfer AM, Hinkle G et al. A lentiviral RNAi library for human and mouse genes applied to an arrayed viral high-content screen. Cell 2006; 124: 1283-1298.
71. Zeng X, Goetz JA, Suber LM, Scott WJ, Schreiner CM, Robbins DJ. A freely diffusible form of Sonic hedgehog mediates long-range signalling. Nature 2001; 411: 716-720.
72. Goetz JA, Singh S, Suber LM, Kull FJ, Robbins DJ. A highly conserved aminoterminal region of sonic hedgehog is required for the formation of its freely diffusible multimeric form. J Biol Chem 2006; 281: 4087-4093.
73. Robbins DJ, Nybakken KE, Kobayashi R, Sisson JC, Bishop JM, Therond PP. Hedgehog elicits signal transduction by means of a large complex containing the kinesin-related protein costal2. Cell 1997; 90: 225-234.
74. Petty WJ, Li N, Biddle A, Bounds R, Nitkin C, Ma Y et al. A novel retinoic acid receptor beta isoform and retinoid resistance in lung carcinogenesis. J Natl Cancer Inst 2005; 97: 1645-1651.
75. Denizot F, Lang R. Rapid colorimetric assay for cell growth and survival. Modifications to the tetrazolium dye procedure giving improved sensitivity and reliability. J Immunol Methods 1986; 89: 271-277.
76. Fernandez C, Tatard VM, Bertrand N, Dahmane N. Differential modulation of Sonic-hedgehog-induced cerebellar granule cell precursor proliferation by the IGF signaling network. Dev Neurosci 2010; 32: 59-70.
77. Wu Z, Irizarry R. Gentleman R, Martinez-Murillo F, Spencer F. A model-based background adjustment for oligonucleotide expression arrays. J Am Stat Assoc 2004; 99: 909-917.
78. Lee E-S, Son D-S, Kim S-H, Lee J, Jo J, Han J et al. Prediction of recurrence-free survival in postoperative non-small cell lung cancer patients by using an integrated model of clinical information and gene expression. Clin Cancer Res 2008; 14: 7397-7404.
79. Kuner R, Muley T, Meister M, Ruschhaupt M, Buness A, Xu EC et al. Global gene expression analysis reveals specific patterns of cell junctions in non-small cell lung cancer subtypes. Lung Cancer 2009; 63: 32-38.