Hedgehog signaling pathway mediates invasion and metastasis of hepatocellular carcinoma via ERK pathway

Acta Pharmacologica Sinica

Volumn 33, Issue 5, 2012, Pages 691-700

  Lu, Jing Tao ^a   Zhao, Wen Di ^a   He, Wei ^a   Wei, Wei ^a  

^a ANHUI MEDICAL UNIVERSITY   (China)

Author keywords

ERK pathway; Hedgehog signaling pathway; Human hepatocellular carcinoma; Invasion and metastasis; MMP 9; Nuclear glioma associated oncogene 1 (Gli1)

Indexed keywords

1,4 DIAMINO 1,4 BIS(2 AMINOPHENYLTHIO) 2,3 DICYANOBUTADIENE; 2 (2 AMINO 3 METHOXYPHENYL)CHROMONE; GELATINASE B; SONIC HEDGEHOG PROTEIN;

ADULT; AGED; ARTICLE; CANCER INVASION; CONTROLLED STUDY; FEMALE; HUMAN; HUMAN CELL; HUMAN TISSUE; IMMUNOHISTOCHEMISTRY; LIVER CELL CARCINOMA; MAJOR CLINICAL STUDY; MALE; METASTASIS; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; WESTERN BLOTTING; WOUND HEALING;

ADULT; AGED; BLOTTING, WESTERN; BUTADIENES; CARCINOMA, HEPATOCELLULAR; CELL LINE, TUMOR; CELL MOVEMENT; CINNAMATES; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; FLAVONOIDS; HEDGEHOG PROTEINS; HUMANS; IMMUNOHISTOCHEMISTRY; LIVER NEOPLASMS; MALE; MAP KINASE SIGNALING SYSTEM; MATRIX METALLOPROTEINASE 9; MIDDLE AGED; MITOGEN-ACTIVATED PROTEIN KINASE 1; MITOGEN-ACTIVATED PROTEIN KINASE 3; NEOPLASM GRADING; NEOPLASM INVASIVENESS; NITRILES; PHOSPHORYLATION; PROTEIN KINASE INHIBITORS; TRANSCRIPTION FACTORS; VERATRUM ALKALOIDS;

EID: 84860709668     PISSN: 16714083     EISSN: 17457254     Source Type: Journal    
DOI: 10.1038/aps.2012.24     Document Type: Article

References (55)

1. Aravalli RN, Steer CJ, Cressman EN. Molecular mechanisms of hepatocellular carcinoma. Hepatology 2008; 48: 2047-63.
2. Walzer N, Kulik LM. Hepatocellular carcinoma: latest developments. Curr Opin Gastroenterol 2008; 24: 312-9. (Pubitemid 351535890)
3. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005; 55: 74-108.
4. Chen XP, Qiu FZ, Wu ZD, Zhang ZW, Huang ZY, Chen YF, et al. Effects of location and extension of portal vein tumor thrombus on long-term outcomes of surgical treatment for hepatocellular carcinoma. Ann Surg Oncol 2006; 13: 940-6.
5. Tang ZY, Ye SL, Liu YK, Qin LX, Sun HC, Ye QH, et al. A decade's studies on metastasis of hepatocellular carcinoma. J Cancer Res Clin Oncol 2004; 130: 187-96.
6. Min L, He B, Hui L. Mitogen-activated protein kinases in hepatocellular carcinoma development. Semin Cancer Biol 2011; 21: 10-20.
7. Hsieh YH, Wu TT, Huang CY, Hsieh YS, Hwang JM, Liu JY. p38 mitogenactivated protein kinase pathway is involved in protein kinase Calpharegulated invasion in human hepatocellular carcinoma cells. Cancer Res 2007; 67: 4320-7.
8. Martínez-López N, Varela-Rey M, Fernández-Ramos D, Woodhoo A, Vázquez-Chantada M, Embade N, et al. Activation of LKB1-Akt pathway independent of phosphoinositide 3-kinase plays a critical role in the proliferation of hepatocellular carcinoma from nonalcoholic steatohepatitis. Hepatology 2010; 52: 1621-31.
9. Whittaker S, Marais R, Zhu AX. The role of signaling pathways in the development and treatment of hepatocellular carcinoma. Oncogene 2010; 29: 4989-5005.
10. Chen JS, Wang Q, Fu XH, Huang XH, Chen XL, Cao LQ, et al. Involvement of PI3K/PTEN/AKT/mTOR pathway in invasion and metastasis in hepatocellular carcinoma: Association with MMP-9. Hepatol Res 2009; 39: 177-86.
11. Wei W, Chua MS, Grepper S, So SK. Blockade of Wnt-1 signaling leads to anti-tumor effects in hepatocellular carcinoma cells. Mol Cancer 2009; 8: 76-81.
12. Kaposi-Novak P, Lee JS, Gòmez-Quiroz L, Coulouarn C, Factor VM, Thorgeirsson SS. Met-regulated expression signature defines a subset of human hepatocellular carcinomas with poor prognosis and aggressive phenotype. J Clin Invest 2006; 116: 1582-95.
13. Horiguchi N, Takayama H, Toyoda M, Otsuka T, Fukusato T, Merlino G, et al. Hepatocyte growth factor promotes hepatocarcinogenesis through c-Met autocrine activation and enhanced angiogenesis in transgenic mice treated with diethylnitrosamine. Oncogene 2002; 21: 1791-9. (Pubitemid 34259181)
14. Ruizi AA, Sanchez P, Dahmane N. Gli and hedgehog in cancer: tumours, embryos and stem cells. Nat Rev Cancer 2002; 2: 361-72. (Pubitemid 37328949)
15. Goetz JA, Suber LM, Zeng X, Robbins DJ. Sonic hedgehog as a mediator of long-range signaling. Bioessays 2002; 24: 157-65. (Pubitemid 34179294)
16. Nybakken K, Perrimon N. Hedgehog signal transduction: recent findings. Curr Opin Genet Dev 2002; 12: 503-11. (Pubitemid 35013531)
17. Sasaki H, Nishizaki Y, Hui C, Nakafuku M, Kondoh H. Regulation of Gli2 and Gli3 activities by an amino-terminal repression domain: implication of Gli2 and Gli3 as primary mediators of Shh signaling. Development 1999; 126: 3915-24. (Pubitemid 29440488)
18. Stepan V, Ramamoorthy S, Nitsche H, Zavros Y, Merchant JL, Todisco A. Regulation and function of the sonic hedgehog signal transduction pathway in isolated gastric parietal cells. J Biol Chem 2005; 280: 15700-8. (Pubitemid 40616689)
19. Ingham PW, McMahon AP. Hedgehog signaling in animal development: paradigms and principles. Genes Dev 2001; 15: 3059-87. (Pubitemid 33115673)
20. Cohen MM Jr. The Hedgehog signaling network. Am J Med Genet 2003; 123A: 5-28. (Pubitemid 37309353)
21. Kump E, Ji J, Wernli M, Häusermann P, Erb P. Gli2 upregulates cFlip and renders basal cell carcinoma cells resistant to death ligandmediated apoptosis. Oncogene 2008; 27: 3856-64. (Pubitemid 351862061)
22. Caro I, Low JA. The role of the hedgehog signaling pathway in the development of basal cell carcinoma and opportunities for treatment. Clin Cancer Res 2010; 16: 3335-9.
23. Bisht S, Brossart P, Maitra A, Feldmann G. Agents targeting the Hedgehog pathway for pancreatic cancer treatment. Curr Opin Investig Drugs 2010; 11: 1387-98.
24. Yoshikawa K, Shimada M, Miyamoto H, Higashijima J, Miyatani T, Nishioka M, et al. Sonic hedgehog relates to colorectal carcinogenesis. J Gastroenterol 2009; 44: 1113-7.
25. Katoh Y, Katoh M. Hedgehog signaling pathway and gastric cancer. Cancer Biol Ther 2005; 4: 1050-4. (Pubitemid 41598556)
26. Velcheti V, Govindan R. Hedgehog signaling pathway and lung cancer. J Thorac Oncol 2007; 2: 7-10. (Pubitemid 47163922)
27. 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: 851-6. (Pubitemid 37355945)
28. Reagan-Shaw S, Cozma D, Thomas-Tikhonenko A, Ahmad N, Spiegelman VS. Role of GLI2 transcription factor in growth and tumorigenicity of prostate cells. Cancer Res 2007; 67: 10642-6. (Pubitemid 350145887)
29. Xu FG, Ma QY, Wang Z. Blockade of hedgehog signaling pathway as a therapeutic strategy for pancreatic cancer. Cancer Lett 2009; 283: 119-24.
30. Haaf AT, Bektas N, von Serenyi S, Losen I, Arweiler EC, Hartmann A, et al. Expression of the glioma-associated oncogene homolog (GLI)1 in human breast cancer is associated with unfavourable overall survival. BMC Cancer 2009; 25: 298-301.
31. Mukherjee S, Frolova N, Sadlonova A, Novak Z, Steg A, Page GP, et al. Hedgehog signaling and response to cyclopamine differ in epithelial and stromal cells in benign breast and breast cancer. Cancer Biol Ther 2006; 5: 674-83. (Pubitemid 44024723)
32. Eichenmüller M, Gruner I, Hagl B, Häberle B, Müller-Höcker J, von Schweinitz D, et al. Blocking the hedgehog pathway inhibits hepatoblastoma growth. Hepatology 2009; 49: 482-90.
33. Ma X, Sheng T, Zhang Y, Zhang X, He J, Huang S, et al. Hedgehog signaling is activated in subsets of esophageal cancers. Int J Cancer 2006; 118: 139-48. (Pubitemid 41681590)
34. Sicklick JK, Li YX, Jayaraman A, Kannangai R, Qi Y, Vivekanandan P, et al. Dysregulation of the Hedgehog pathway in human hepatocarcinogenesis. Carcinogenesis 2006; 27: 748-57.
35. Huang S, He J, Zhang X, Bian Y, Yang L, Xie G, et al. Activation of the hedgehog pathway in human hepatocellular carcinomas. Carcinogenesis 2006; 27: 1334-40. (Pubitemid 43985408)
36. Cheng WT, Xu K, Tian DY, Zhang ZG, Liu LJ, Chen Y. Role of hedgehog signaling pathway in proliferation and invasiveness of hepatocellular carcinoma cells. Int J Oncol 2009; 34:829-36.
37. Tada M, Kanai F, Tanaka Y, Tateishi K, Ohta M, Asaoka Y, et al. Downregulation of hedgehog-interacting protein through genetic and epigenetic alterations in human hepatocellular carcinoma. Clin Cancer Res 2008; 14: 3768-76.
38. Kim Y, Yoon JW, Xiao X, Dean NM, Monia BP, Marcusson EG. Selective down-regulation of glioma-associated oncogene 2 inhibits the proliferation of hepatocellular carcinoma cells. Cancer Res 2007; 67: 3583-93. (Pubitemid 46762142)
39. Kim HY, Cho HK, Hong SP, Cheong J. Hepatitis B virus X protein stimulates the Hedgehog-Gli activation through protein stabilization and nuclear localization of Gli1 in liver cancer cells. Cancer Lett 2011; 309: 176-84.
40. Chen X, Lingala S, Khoobyari S, Nolta J, Zern MA, Wu J. Epithelial mesenchymal transition and hedgehog signaling activation are associated with chemoresistance and invasion of hepatoma subpopulations. J Hepatol 2010; 55: 838-45.
41. Zheng X, Yao Y, Xu Q, Tu K, Liu Q. Evaluation of glioma-associated oncogene 1 expression and its correlation with the expression of sonic hedgehog, E-cadherin and S100a4 in human hepatocellular carcinoma. Mol Med Report 2010; 3: 965-70.
42. Philips GM, Chan IS, Swiderska M, Schroder VT, Guy C, Karaca GF, et al. Hedgehog signaling antagonist promotes regression of both liver fibrosis and hepatocellular carcinoma in a murine model of primary liver cancer. PLoS One 2011; 6: e23943.
43. Elia D, Madhala D, Ardon E, Reshef R, Halevy O. Sonic hedgehog promotes proliferation and differentiation of adult muscle cells: Involvement of MAPK/ERK and PI3K/Akt pathways. Biochim Biophys Acta 2007; 1773: 1438-46. (Pubitemid 47374851)
44. Schnidar H, Eberl M, Klingler S, Mangelberger D, Kasper M, Hauser-Kronberger C, et al. Epidermal growth factor receptor signaling synergizes with Hedgehog/GLI in oncogenic transformation via activation of the MEK/ERK/JUN pathway. Cancer Res 2009; 69: 1284-92.
45. Chang H, Li Q, Moraes RC, Lewis MT, Hamel PA. Activation of ERK by sonic hedgehog is independent of canonical hedgehog signaling. Int J Biochem Cell Biol 2010; 42: 1462-71.
46. Seto M, Ohta M, Asaoka Y, Ikenoue T, Tada M, Miyabayashi K, et al. Regulation of the hedgehog signaling by the mitogen-activated protein kinase cascade in gastric cancer. Mol Carcinog 2009; 48: 703-12.
47. Donadio AC, Remedi MM, Susperreguy S, Frede S, Gilardoni MB, Tang Y, et al. Extracellular matrix metalloproteinase inducer and matrix metalloproteinases (MMPs) as regulators of tumor-host interaction in a spontaneous metastasis model in rats. Histochem Cell Biol 2008; 130: 1155-64.
48. Cortes-Reynosa P, Robledo T, Macias-Silva M, Wu SV, Salazar EP. Src kinase regulates metalloproteinase-9 secretion induced by type IV collagen in MCF-7 human breast cancer cells. Matrix Biol 2008; 27: 220-31. (Pubitemid 351375390)
49. Wang K, Pan L, Che X, Cui D, Li C. Sonic Hedgehog/GLI signaling pathway inhibition restricts cell migration and invasion in human gliomas. Neurol Res 2010; 32: 975-80.
50. Onishi H, Kai M, Odate S, Iwasaki H, Morifuji Y, Ogino T, et al. Hypoxia activates the hedgehog signaling pathway in a ligand-independent manner by upregulation of Smo transcription in pancreatic cancer. Cancer Sci 2011; 102: 1144-50.
51. Huang XH, Chen JS, Wang Q, Chen XL, Wen L, Chen LZ, et al. miR-338-3p suppresses invasion of liver cancer cell by targeting smoothened. J Pathol 2011; 225: 463-72.
52. Thorgeirsson SS, Grisham JW. Molecular pathogenesis of human hepatocellular carcinoma. Nat Genet 2002; 31: 339-46. (Pubitemid 35154440)
53. Thomas MB, Zhu AX. Hepatocellular carcinoma: the need for progress. J Clin Oncol 2005; 23: 2892-9. (Pubitemid 46224106)
54. Grieco A, Pompili M, Caminiti G, Miele L, Covino M, Alfei B, et al. Prognostic factors for survival in patients with early-intermediate hepatocellular carcinoma undergoing non-surgical therapy: comparison of Okuda, CLIP, and BCLC staging systems in a single Italian centre. Gut 2005; 54: 411-8. (Pubitemid 40299100)
55. Kessenbrock K, Plaks V, Werb Z. Matrix metalloproteinases: regulators of the tumor microenvironment. Cell 2010; 141: 52-67.