ILK overexpression in human hepatocellular carcinoma and liver cirrhosis correlates with activation of Akt

Oncology Reports

Volumn 20, Issue 6, 2008, Pages 1337-1344

  Peroukides, Stavros ^a   Bravou, Vasiliki ^a   Varakis, John ^a   Alexopoulus, Alexandros ^a   Kalofonos, Haralabos ^a   Papadaki, Helen ^a  

^a UNIVERSITY OF PATRAS   (Greece)

Author keywords

catenin; Cirrhosis; E cadherin; Hepatocellular carcinoma; Integrin linked kinase; Phosphorylated Akt

Indexed keywords

BETA CATENIN; INTEGRIN LINKED KINASE; PROTEIN KINASE B; UVOMORULIN; INTEGRIN-LINKED KINASE; PROTEIN SERINE THREONINE KINASE; UNCLASSIFIED DRUG;

ARTICLE; CONTROLLED STUDY; DISEASE ASSOCIATION; DOWN REGULATION; ENZYME ACTIVATION; HUMAN; HUMAN TISSUE; IMMUNOHISTOCHEMISTRY; LIVER CELL CARCINOMA; LIVER CIRRHOSIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; RISK FACTOR; BIOLOGICAL MODEL; BIOSYNTHESIS; ENZYMOLOGY; FIBROSIS; GENE EXPRESSION REGULATION; LIVER; LIVER CELL; LIVER TUMOR; METABOLISM; PATHOLOGY; PHOSPHORYLATION; PHYSIOLOGY;

BETA CATENIN; CARCINOMA, HEPATOCELLULAR; ENZYME ACTIVATION; FIBROSIS; GENE EXPRESSION REGULATION, ENZYMOLOGIC; GENE EXPRESSION REGULATION, NEOPLASTIC; HEPATOCYTES; HUMANS; LIVER; LIVER NEOPLASMS; MODELS, BIOLOGICAL; PHOSPHORYLATION; PROTEIN-SERINE-THREONINE KINASES; PROTO-ONCOGENE PROTEINS C-AKT;

EID: 59249084505     PISSN: 1021335X     EISSN: 17912431     Source Type: Journal    
DOI: 10.3892/or_00000149     Document Type: Article

References (43)

1. McGlynn KA and London WT: Epidemiology and natural history of hepatocellular carcinoma. Best Pract Res Clin Gastroenterol 19: 3-23, 2005.
2. Persad S and Dedhar S: The role of integrin-linked kinase (ILK) in cancer progression. Cancer Metastasis Rev 22: 375-384, 2003.
3. Attwell S, Mills J, Troussard A, Wu C and Dedhar S: Integration of cell attachment, cytoskeletal localization, and signaling by integrin-linked kinase (ILK), CH-ILKBP, and the tumor suppressor PTEN. Mol Cell Biol 14: 4813-4825, 2003.
4. D'Amico M, Hulit J, Amanatullah DF, Zafonte BT, Albanese C, Bouzahzah B, Fu M, Augenlicht LH, Donehower LA, Takemaru K, Moon RT, Davis R, Lisanti MP, Shtutman M, Zhurinsky J, Ben-Ze'ev A, Troussard AA, Dedhar S and Pestell RG: The integrin-linked kinase regulates the cyclin D1 gene through glycogen synthase kinase 3β and cAMP-responsive element binding protein-dependent pathways. J Biol Chem 275: 32649-32657, 2000.
5. Radeva G, Petrocelli T, Behrend E, Leung-Hagesteijn C, Filmus J, Slingerland J and Dedhar S: Overexpression of the integrin-linked kinase promotes anchorage-independent cell cycle progression. J Biol Chem 272: 13937-13944, 1997.
6. Persad S, Attwell S, Gray V, Delcommenne M, Troussard A, Sanghera J and Dedhar S: Inhibition of integrin-linked kinase (ILK) suppresses activation of protein kinase by Akt and induces cell cycle arrest and apoptosis of PTEN-mutant prostate cancer cells. Proc Natl Acad Sci USA 97: 3207-3212, 2000.
7. Oloumi A, McPhee T and Dedhar S: Regulation of E-cadherin expression and β-catenin/Tcf transcriptional activity by the integrin-linked kinase. Biochim Biophys Acta 1691: 1-15, 2004.
8. Merle P, Kim M, Herrmann M, Gupte A, Lefrançois L, Califano S, Trépo C, Tanaka S, Vitvitski L, de la Monte S and Wands JR: Oncogenic role of the frizzled-7/β-catenin pathway in hepatocellular carcinoma. J Hepatol 43: 854-862, 2005.
9. Pinkse G, Jiawan-Lalai R, Bruijn J and De Heer E: RGD peptides confer survival to hepatocytes via the β1-integrin-ILK-pAkt pathway. J Hepatol 42: 87-93, 2005.
10. Persad S, Attwell S, Gray V, Mawji N, Deng JT, Leung D, Yan J, Sanghera J, Walsh MP and Dedhar S: Regulation of protein kinase B/Akt-serine 473 phosphorylation by integrin-linked kinase. J Biol Chem 276: 27462-27469, 2001.
11. Graff J, Deddens J and Konicek B: Integrin-linked kinase expression increases with prostate tumor grade. Clin Cancer Res 7: 1987-1991, 2001.
12. Bravou V, Klironomos G, Papadaki E, Taraviras S and Varakis J: ILK over-expression in human colon cancer progression correlates with activation of β-catenin, down-regulation of E-cadherin and activation of the Akt-FKHR pathway. J Pathol 208: 91-99, 2006.
13. Ahmed N, Riley C, Oliva K, Stutt E, Rice G and Quinn M: Integrin-linked kinase expression increases with ovarian tumor grade and is sustained by peritoneal tumor fluid. J Pathol 201: 229-237, 2003.
14. Dai DL, Makretsov N, Campos EI, Huang C, Zhou Y, Huntsman D, Martinka M and Li G: Increased expression of integrin-linked kinase is correlated with melanoma progression and poor patient survival. Clin Cancer Res 9: 4409-4414, 2003.
15. Su JM, Wang LY, Liang YL and Zha XL: Role of cell adhesion signal molecules in hepatocellular carcinoma cell apoptosis. World J Gastroenterol 11: 4667-4673, 2005.
16. Shafiei MS and Rockey DC: The role of integrin-linked kinase in liver wound healing. J Biol Chem 281: 24863-24872, 2006.
17. Plante I, Cyr D and Charbonneau M: Involvement of the integrin-linked kinase pathway in hexachlorobenzene-induced genderspecific rat hepatocarcinogenesis. Toxicol Sci 88: 346-357, 2005.
18. Intaraprasong P, Assi K, Owen DA, Huntsman DG, Chung SW, Scudamore CH, Yoshida EM and Salh B: Expression of integrin-linked kinase is not a useful prognostic marker in resected hepatocellular cancer. Anticancer Res 27: 4371-4376, 2007.
19. Yoganathan N, Costello P, Chen X, Jabali M, Yan J, Leung D, Zhang Z, Yee A, Dedhar S and Sanghera J: Integrin-linked kinase (ILK): A 'hot' therapeutic target. Biochem Pharmacol 60: 1115-1119, 2000.
20. Ito R, Oue N, Zhu X, Yoshida K, Nakayama H, Yokozaki H and Yasui W: Expression of integrin-linked kinase is closely correlated with invasion and metastasis of gastric carcinoma. Virch Arch 442: 118-123, 2003.
21. Okamura M, Yamaji S, Nagashima Y, Nishikawa M, Yoshimoto N, Kido Y, Iemoto Y, Aoki I and Ishigatsubo Y: Prognostic value of integrin β1-ILK-pAkt signalling pathway in non-small cell lung cancer. Hum Pathol 38: 1081-1091, 2007.
22. Friedman S: Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury. J Biol Chem 275: 2247-2250, 2000.
23. Zhang Y, Ikegami T, Honda A, Miyazaki T, Bouscarel B, Rojkind M, Hyodo I and Matsuzaki Y: Involvement of integrin-linked kinase in carbon tetrachloride-induced hepatic fibrosis in rats. Hepatology 44: 612-622, 2006.
24. Li Y, Yang J, Dai C, Wu C and Liu Y: Role for integrin-linked kinase in mediating tubular epithelial to mesenchymal transition and renal interstitial fibrogenesis. J Clin Invest 112: 503-516, 2003.
25. Lawlor M and Alessi D: PKB/Akt: a key mediator of cell proliferation, survival and insulin responses? J Cell Sci 114: 2903-2910, 2001.
26. Singh R and Czaja M: Capitalizing on AKT signaling to inhibit hepatocellular carcinoma cell proliferation. Cancer Biol Ther 4: 1240-1247, 2005.
27. Nakanishi K, Sakamoto M, Yamasaki S, Todo S and Hirohashi S: Akt phosphorylation is a risk factor for early disease recurrence and poor prognosis in hepatocellular carcinoma. Cancer 103: 307-312, 2005.
28. Bralet MP, R'egimbeau JM, Pineau P, Dubois S, Loas G, Degos F, Valla D, Belghiti J, Degott C and Terris B: Hepatocellular carcinoma occurring in nonfibrotic liver: epidemiologic and histopathologic analysis of 80 French cases. Hepatology 32: 200-204, 2000.
29. Troussard AA, McDonald PC, Wederell ED, Mawji NM, Filipenko NR, Gelmon KA, Kucab JE, Dunn SE, Emerman JT, Bally MB and Dedhar S: Preferential dependence of breast cancer cells versus normal cells on integrin-linked kinase for protein kinase B/Akt activation and cell survival. Cancer Res 66: 393-403, 2006.
30. Troussard A, Mawji N, Ong C, Mui A, Arnaud R and Dedhar S: Conditional knock-out of integrin-linked kinase demonstrates an essential role in protein kinase B/Akt activation. J Biol Chem 278: 22374-22378, 2003.
31. Adachi M, Osawa Y, Uchinami H, Kitamura T, Accili D and Brenner D: The forkhead transcription factor FoxO1 regulates proliferation and transdifferentiation of hepatic stellate cells. Gastroenterology 132: 1434-1446, 2007.
32. Reif S, Lang A, Lindquist JN, Yata Y, Gabele E, Scanga A, Brenner DA and Rippe RA: The role of focal adhesion kinase phosphatidylinositol 3-kinase-Akt signaling in hepatic stellate cell proliferation and type I collagen expression. J Biol Chem 278: 8083-8090, 2003.
33. Tan C, Mui A and Dedhar S: The integrin linked kinase (ILK) regulates inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in a NF-κB dependent manner. J Biol Chem 277: 3109-3116, 2002.
34. Liu E, Sinha S, Williams C, Cyrille M, Heller E, Snapper SB, Georgopoulos K, St-Arnaud R, Force T, Dedhar S and Gerszten RE: Targeted deletion of integrin-linked kinase reveals a role in T-cell chemotaxis and survival. Mol Cell Biol 25: 11145-11155, 2005.
35. Hino O, Kajino K, Umeda T and Arakawa Y: Understanding the hypercarcinogenic state in chronic hepatitis: a clue to the prevention of human hepatocellular carcinoma. J Gastroenterology 37: 883-887, 2002.
36. Inagawa S, Itabashi M, Adachi S, Kawamoto T, Hori M, Shimazaki J, Yoshimi F and Fukao K: Expression and prognostic roles of β-catenin in hepatocellular carcinoma: Correlation with tumor progression and postoperative survival. Clin Cancer Res 8: 450-456, 2002.
37. Prange W, Breuhahn K, Fischer F, Zilkens C, Pietsch T, Petmecky K, Eilers R, Dienes HP and Schirmacher P: Betacatenin accumulation in the progression of human hepatocarcinogenesis correlates with loss of E-cadherin and accumulation of p53, but not with expression of conventional WNT-1 target genes. J Pathol 201: 250-259, 2003.
38. Suzuki T, Yano H, Nakashima Y, Nakashima O and Kojiro M: β-catenin expression in hepatocellular carcinoma: A possible participation of β-catenin in the dedifferentiation process. J Gastroenterol Hepatol 17: 994-1000, 2002.
39. Inayoshi J, Ichida T, Sugitani S, Tsuboi Y, Genda T, Honma N and Asakura H: Gross appearance of hepatocellular carcinoma reflects E-cadherin expression and risk of early recurrence after surgical treatment. J Gastroenterol Hepatol 18: 673-677, 2003.
40. Novak A, Hsu SC, Leung-Hagensteun C, Radeva G, Papkoff J, Montesano R, Roskelley C, Grosschedl R and Dedhar S: Cell adhesion and the integrin-linked kinase regulate the LEF-1 and β-catenin signaling pathways. Proc Natl Acad Sci USA 95: 4374-4379, 1998.
41. Wong C, Fan S and Ng I: β-catenin mutation and overexpression in hepatocellular carcinoma, clinicopathologic and prognostic significance. Cancer 92: 136-145, 2001.
42. Matsumura T, Makino R and Mitamura K: Frequent downregulation of E-cadherin by genetic and epigenetic changes in the malignant progression of hepatocellular carcinomas. Clin Cancer Res 7: 594-599, 2001.
43. Kanai Y, Ushijima S, Tsuda H, Sakamoto M and Hirohashi S: Aberrant DNA methylation precedes loss of heterozygosity on chromosome 16 in chronic hepatitis and liver cirrhosis. Cancer Lett 148: 73-80, 2000.