Hedgehog signaling antagonist GDC-0449 (Vismodegib) inhibits pancreatic cancer stem cell characteristics: Molecular mechanisms

PLoS ONE

Volumn 6, Issue 11, 2011, Pages

  Singh, Brahma N ^a   Fu, Junsheng ^a   Srivastava, Rakesh K ^a   Shankar, Sharmila ^a  

^a UNIVERSITY OF KANSAS CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CASPASE 3; CELL DNA; DEATH RECEPTOR 4; DEATH RECEPTOR 5; FAS ANTIGEN; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE; PLATELET DERIVED GROWTH FACTOR ALPHA RECEPTOR; PROTEIN BCL 2; SHORT HAIRPIN RNA; SONIC HEDGEHOG PROTEIN; TRANSCRIPTION FACTOR GLI1; TRANSCRIPTION FACTOR GLI2; VISMODEGIB; ANILIDE; G PROTEIN COUPLED RECEPTOR; PYRIDINE DERIVATIVE; SMO PROTEIN, HUMAN; TRANSCRIPTION FACTOR;

ANTIGEN EXPRESSION; ARTICLE; CANCER CELL CULTURE; CANCER INHIBITION; CANCER STEM CELL; CELL SURVIVAL; CELL VIABILITY; CONTROLLED STUDY; DOWN REGULATION; DRUG MECHANISM; ENZYME ACTIVATION; GENE; GENE ACTIVATION; GENE EXPRESSION; GLI GENE; HUMAN; HUMAN CELL; IN VITRO STUDY; PANCREAS CANCER; PROTEIN CLEAVAGE; PROTEIN DNA BINDING; SIGNAL TRANSDUCTION; TUMOR SPHEROID; UPREGULATION; APOPTOSIS; DRUG ANTAGONISM; DRUG EFFECT; PANCREAS TUMOR; PATHOLOGY; TUMOR CELL LINE;

ERINACEIDAE;

ANILIDES; APOPTOSIS; CELL LINE, TUMOR; CELL SURVIVAL; HEDGEHOG PROTEINS; HUMANS; NEOPLASTIC STEM CELLS; PANCREATIC NEOPLASMS; PYRIDINES; RECEPTORS, G-PROTEIN-COUPLED; SIGNAL TRANSDUCTION; TRANSCRIPTION FACTORS;

EID: 80555145216     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0027306     Document Type: Article

References (50)

1. Warshaw AL, (1991) Implications of peritoneal cytology for staging of early pancreatic cancer. Am J Surg 161: 26-29; discussion 29-30.
2. Li D, Xie K, Wolff R, Abbruzzese JL, (2004) Pancreatic cancer. Lancet 363: 1049-1057.
3. Burris HA, 3rd, Moore MJ, Andersen J, Green MR, Rothenberg ML, et al. (1997) Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 15: 2403-2413.
4. Ogden SK, Ascano M Jr, Stegman MA, Robbins DJ, (2004) Regulation of Hedgehog signaling: a complex story. Biochem Pharmacol 67: 805-814.
5. Yauch RL, Gould SE, Scales SJ, Tang T, Tian H, et al. (2008) A paracrine requirement for hedgehog signalling in cancer. Nature 455: 406-410.
6. Teglund S, Toftgard R, (2010) Hedgehog beyond medulloblastoma and basal cell carcinoma. Biochim Biophys Acta 1805: 181-208.
7. Eggenschwiler JT, Anderson KV, (2007) Cilia and developmental signaling. Annu Rev Cell Dev Biol 23: 345-373.
8. Scales SJ, de Sauvage FJ, (2009) Mechanisms of Hedgehog pathway activation in cancer and implications for therapy. Trends Pharmacol Sci 30: 303-312.
9. Nolan-Stevaux O, Lau J, Truitt ML, Chu GC, Hebrok M, et al. (2009) GLI1 is regulated through Smoothened-independent mechanisms in neoplastic pancreatic ducts and mediates PDAC cell survival and transformation. Genes Dev 23: 24-36.
10. Ingham PW, McMahon AP, (2001) Hedgehog signaling in animal development: paradigms and principles. Genes Dev 15: 3059-3087.
11. Olive KP, Jacobetz MA, Davidson CJ, Gopinathan A, McIntyre D, et al. (2009) Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Science 324: 1457-1461.
12. Ruiz i Altaba A, (2008) Therapeutic inhibition of Hedgehog-GLI signaling in cancer: epithelial, stromal, or stem cell targets? Cancer Cell 14: 281-283.
13. Hidalgo M, Maitra A, (2009) The hedgehog pathway and pancreatic cancer. N Engl J Med 361: 2094-2096.
14. Tang SN, Fu J, Nall D, Rodova M, Shankar S, et al. (2011) Inhibition of sonic hedgehog pathway and pluripotency maintaining factors regulate human pancreatic cancer stem cell characteristics. Int J Cancer.
15. Ruiz i Altaba A, (1999) Gli proteins and Hedgehog signaling: development and cancer. Trends Genet 15: 418-425.
16. Bian YH, Huang SH, Yang L, Ma XL, Xie JW, et al. (2007) Sonic hedgehog-Gli1 pathway in colorectal adenocarcinomas. World J Gastroenterol 13: 1659-1665.
17. Dahmane N, Sanchez P, Gitton Y, Palma V, Sun T, et al. (2001) The Sonic Hedgehog-Gli pathway regulates dorsal brain growth and tumorigenesis. Development 128: 5201-5212.
18. Gerber AN, Wilson CW, Li YJ, Chuang PT, (2007) The hedgehog regulated oncogenes Gli1 and Gli2 block myoblast differentiation by inhibiting MyoD-mediated transcriptional activation. Oncogene 26: 1122-1136.
19. Kasper M, Regl G, Frischauf AM, Aberger F, (2006) GLI transcription factors: mediators of oncogenic Hedgehog signalling. Eur J Cancer 42: 437-445.
20. Lee J, Wu X, Pasca di Magliano M, Peters EC, Wang Y, et al. (2007) A small-molecule antagonist of the hedgehog signaling pathway. Chembiochem 8: 1916-1919.
21. Liu H, Gu D, Xie J, (2011) Clinical implications of hedgehog signaling pathway inhibitors. Chin J Cancer 30: 13-26.
22. Xie J, (2008) Hedgehog signaling pathway: development of antagonists for cancer therapy. Curr Oncol Rep 10: 107-113.
23. Stecca B, Mas C, Clement V, Zbinden M, Correa R, et al. (2007) Melanomas require HEDGEHOG-GLI signaling regulated by interactions between GLI1 and the RAS-MEK/AKT pathways. Proc Natl Acad Sci U S A 104: 5895-5900.
24. Sanchez P, Hernandez AM, Stecca B, Kahler AJ, DeGueme AM, et al. (2004) Inhibition of prostate cancer proliferation by interference with SONIC HEDGEHOG-GLI1 signaling. Proc Natl Acad Sci U S A 101: 12561-12566.
25. Katoh Y, Katoh M, (2009) Integrative genomic analyses on GLI1: positive regulation of GLI1 by Hedgehog-GLI, TGFbeta-Smads, and RTK-PI3K-AKT signals, and negative regulation of GLI1 by Notch-CSL-HES/HEY, and GPCR-Gs-PKA signals. Int J Oncol 35: 187-192.
26. Yoshikawa N, Yamada J, Tsuno NH, Okaji Y, Kawai K, et al. (2009) Plaunotol and geranylgeraniol induce caspase-mediated apoptosis in colon cancer. J Surg Res 153: 246-253.
27. Varnat F, Duquet A, Malerba M, Zbinden M, Mas C, et al. (2009) Human colon cancer epithelial cells harbour active HEDGEHOG-GLI signalling that is essential for tumour growth, recurrence, metastasis and stem cell survival and expansion. EMBO Mol Med 1: 338-351.
28. Hashimoto-Torii K, Motoyama J, Hui CC, Kuroiwa A, Nakafuku M, et al. (2003) Differential activities of Sonic hedgehog mediated by Gli transcription factors define distinct neuronal subtypes in the dorsal thalamus. Mech Dev 120: 1097-1111.
29. Shi T, Mazumdar T, Devecchio J, Duan ZH, Agyeman A, et al. (2010) cDNA microarray gene expression profiling of hedgehog signaling pathway inhibition in human colon cancer cells. PLoS One 5.
30. Hwang JH, Lee SH, Lee KH, Lee KY, Kim H, et al. (2009) Cathepsin B is a target of Hedgehog signaling in pancreatic cancer. Cancer Lett 273: 266-272.
31. Hutchin ME, Kariapper MS, Grachtchouk M, Wang A, Wei L, et al. (2005) Sustained Hedgehog signaling is required for basal cell carcinoma proliferation and survival: conditional skin tumorigenesis recapitulates the hair growth cycle. Genes Dev 19: 214-223.
32. Grachtchouk M, Mo R, Yu S, Zhang X, Sasaki H, et al. (2000) Basal cell carcinomas in mice overexpressing Gli2 in skin. Nat Genet 24: 216-217.
33. Shankar S, Nall D, Tang SN, Meeker D, Passarini J, et al. (2011) Resveratrol inhibits pancreatic cancer stem cell characteristics in human and KrasG12D transgenic mice by inhibiting pluripotency maintaining factors and epithelial-mesenchymal transition. PLoS One 6: e16530.
34. Srivastava RK, Tang SN, Zhu W, Meeker D, Shankar S, (2011) Sulforaphane synergizes with quercetin to inhibit self-renewal capacity of pancreatic cancer stem cells. Front Biosci (Elite Ed) 3: 515-528.
35. Mantamadiotis T, Taraviras S, (2011) Self-renewal mechanisms in neural cancer stem cells. Front Biosci 16: 598-607.
36. Lauth M, Toftgard R, (2007) The Hedgehog pathway as a drug target in cancer therapy. Curr Opin Investig Drugs 8: 457-461.
37. Feldmann G, Fendrich V, McGovern K, Bedja D, Bisht S, et al. (2008) An orally bioavailable small-molecule inhibitor of Hedgehog signaling inhibits tumor initiation and metastasis in pancreatic cancer. Mol Cancer Ther 7: 2725-2735.
38. Vogt A, Chuang PT, Hebert J, Hwang J, Lu Y, et al. (2004) Immunoprevention of basal cell carcinomas with recombinant hedgehog-interacting protein. J Exp Med 199: 753-761.
39. Ward RJ, Lee L, Graham K, Satkunendran T, Yoshikawa K, et al. (2009) Multipotent CD15+ cancer stem cells in patched-1-deficient mouse medulloblastoma. Cancer Res 69: 4682-4690.
40. Thiyagarajan S, Bhatia N, Reagan-Shaw S, Cozma D, Thomas-Tikhonenko A, et al. (2007) Role of GLI2 transcription factor in growth and tumorigenicity of prostate cells. Cancer Res 67: 10642-10646.
41. Mazumdar T, DeVecchio J, Shi T, Jones J, Agyeman A, et al. (2011) Hedgehog signaling drives cellular survival in human colon carcinoma cells. Cancer Res 71: 1092-1102.
42. Ruiz i Altaba A, Stecca B, Sanchez P, (2004) Hedgehog-Gli signaling in brain tumors: stem cells and paradevelopmental programs in cancer. Cancer Lett 204: 145-157.
43. Ecke I, Petry F, Rosenberger A, Tauber S, Monkemeyer S, et al. (2009) Antitumor effects of a combined 5-aza-2'deoxycytidine and valproic acid treatment on rhabdomyosarcoma and medulloblastoma in Ptch mutant mice. Cancer Res 69: 887-895.
44. Vorechovsky I, Benediktsson KP, Toftgard R, (1999) The patched/hedgehog/smoothened signalling pathway in human breast cancer: no evidence for H133Y SHH, PTCH and SMO mutations. Eur J Cancer 35: 711-713.
45. Von Hoff DD, LoRusso PM, Rudin CM, Reddy JC, Yauch RL, et al. (2009) Inhibition of the hedgehog pathway in advanced basal-cell carcinoma. N Engl J Med 361: 1164-1172.
46. Jones S, Zhang X, Parsons DW, Lin JC, Leary RJ, et al. (2008) Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 321: 1801-1806.
47. Clement V, Sanchez P, de Tribolet N, Radovanovic I, Ruiz i Altaba A, (2007) HEDGEHOG-GLI1 signaling regulates human glioma growth, cancer stem cell self-renewal, and tumorigenicity. Curr Biol 17: 165-172.
48. Marchese R, Muleti A, Pasqualetti P, Bucci B, Stigliano A, et al. (2006) Low correspondence between K-ras mutations in pancreatic cancer tissue and detection of K-ras mutations in circulating DNA. Pancreas 32: 171-177.
49. Regl G, Kasper M, Schnidar H, Eichberger T, Neill GW, et al. (2004) Activation of the BCL2 promoter in response to Hedgehog/GLI signal transduction is predominantly mediated by GLI2. Cancer Res 64: 7724-7731.
50. Wiznerowicz M, Trono D, (2003) Conditional suppression of cellular genes: lentivirus vector-mediated drug-inducible RNA interference. J Virol 77: 8957-8961.