The complex relationship between liver cancer and the cell cycle: A story of multiple regulations

Cancers

Volumn 6, Issue 1, 2014, Pages 79-111

  Bisteau, Xavier ^a   Caldez, Matias J ^a,b   Kaldis, Philipp ^a,b  

^a INSTITUTE OF MOLECULAR AND CELL BIOLOGY   (Singapore)

^b NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

Author keywords

Cancer; Cell cycle; CKI; Cyclin dependent kinases; Cyclins; Hepatocellular carcinoma; Liver

Indexed keywords

CYCLIN D1; CYCLIN DEPENDENT KINASE; CYCLIN DEPENDENT KINASE 1; CYCLIN DEPENDENT KINASE 2; CYCLIN DEPENDENT KINASE 4; CYCLIN DEPENDENT KINASE 6; CYCLIN E; CYCLINE; PALBOCICLIB; PROTEIN P16; PROTEIN P21; PROTEIN P27; PROTEIN P53; RAS PROTEIN; RETINOBLASTOMA PROTEIN; ROSCOVITINE; S PHASE KINASE ASSOCIATED PROTEIN 2; SORAFENIB;

ADVANCED CANCER; APOPTOSIS; CELL CYCLE PROGRESSION; CELL CYCLE REGULATION; CELL DEATH; CELL PROLIFERATION; GENOMIC INSTABILITY; HUMAN; LIVER CANCER; LIVER CARCINOGENESIS; LIVER CELL; LIVER CELL CARCINOMA; LIVER FIBROSIS; LIVER REGENERATION; LIVER STRUCTURE; NONHUMAN; ONCOGENE; POLYPLOIDY; REVIEW; TUMOR SUPPRESSOR GENE;

EID: 84893366848     PISSN: None     EISSN: 20726694     Source Type: Journal    
DOI: 10.3390/cancers6010079     Document Type: Review

References (229)

1. Washabau, R.J. Chapter 61-Liver. In Canine and Feline Gastroenterology; Chandlers, M.L., Steiner, J.M., Syring, R.J., Twedt, D.C., Wahsabau, R.J., Willard, M.D., Eds.; Saunders-Elsevier Inc.: St. Louis, MO, USA, 2013; pp. 849-957.
2. Hayat, M.A. Liver Carcinoma. Handbook of Immunohistochemistry and in Situ Hybridization of Human Carcinomas; Elsevier Academia Press: Burlington, MA, USA, 2005; Volume 3, pp. 131-151.
3. Rissler, P.; Torndal, U.B.; Eriksson, L.C. Induced drug resistance inhibits selection of initiated cells and cancer development. Carcinogenesis 1997, 18, 649-655.
4. Yusuf, A.; Rao, P.M.; Rajalakshmi, S.; Sarma, D.S. Development of resistance during the early stages of experimental liver carcinogenesis. Carcinogenesis 1999, 20, 1641-1644.
5. Jemal, A.; Bray, F.; Center, M.M.; Ferlay, J.; Ward, E.; Forman, D. Global cancer statistics. CA Cancer J. Clin. 2011, 61, 69-90.
6. Ferlay, J.; Shin, H.-R.; Bray, F.; Forman, D.; Mathers, C.; Parkin, D.M. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int. J. Cancer 2010, 127, 2893-2917.
7. Tabor, E. Hepatocellular carcinoma: Global epidemiology. Dig. Liver Dis. 2001, 33, 115-117.
8. Costanza, C.; Selim, K. Hepatocellular Carcinoma (HCC). In Encyclopedia of Gastroenterology; Johnson, L., Ed.; Elsevier Inc.: New York, NY, USA, 2004; pp. 340-346.
9. Kew, M.C. Liver cancer. Int. Encycl. Public Health 2008, 4, 105-114.
10. McGlynn, K.A.; London, W.T. Epidemiology and natural history of hepatocellular carcinoma. Best Pract. Res. Clin. Gastroenterol. 2005, 19, 3-23.
11. Fattovich, G.; Stroffolini, T.; Zagni, I.; Donato, F. Hepatocellular carcinoma in cirrhosis: Incidence and risk factors. Gastroenterology 2004, 127, S35-S50.
12. Hassan, M.M.; Hwang, L.-Y.; Hatten, C.J.; Swaim, M.; Li, D.; Abbruzzese, J.L.; Beasley, P.; Patt, Y.Z. Risk factors for hepatocellular carcinoma: Synergism of alcohol with viral hepatitis and diabetes mellitus. Hepatology 2002, 36, 1206-1213.
13. El-Serag, H.B. Hepatocellular carcinoma. N. Engl. J. Med. 2011, 365, 1118-1127.
14. Bluteau, O.; Beaudoin, J.-C.; Pasturaud, P.; Belghiti, J.; Franco, D.; Bioulac-Sage, P.; Laurent-Puig, P.; Zucman Rossi, J. Specific association between alcohol intake, high grade of differentiation and 4q34-q35 deletions in hepatocellular carcinomas identified by high resolution allelotyping. Oncogene 2002, 21, 1225-1232.
15. Yakicier, M.C.; Legoix, P.; Vaury, C.; Gressin, L.; Tubacher, E.; Capron, F.; Bayer, J.; Degott, C.; Balabaud, C.; Zucman-Rossi, J. Identification of homozygous deletions at chromosome 16q23 in aflatoxin B1 exposed hepatocellular carcinoma. Oncogene 2001, 20, 5232-5238.
16. Fattovich, G.; Bortolotti, F.; Donato, F. Natural history of chronic hepatitis B: Special emphasis on disease progression and prognostic factors. J. Hepatol. 2008, 48, 335-352.
17. Chuang, S.-C.; la Vecchia, C.; Boffetta, P. Liver cancer: Descriptive epidemiology and risk factors other than HBV and HCV infection. Cancer Lett. 2009, 286, 9-14.
18. El-Serag, H.B.; Rudolph, K.L. Hepatocellular carcinoma: Epidemiology and molecular carcinogenesis. Gastroenterology 2007, 132, 2557-2576.
19. El-Serag, H.B.; Lechel, A.; Rudolph, K.L. Epidemiology and Molecular Mechanisms of Hepatocarcinogenesis. In Zakim and Boyer's Hepatology: A Textbook of Liver Disease, 6th ed.; Boyer, T.D., Manns, M.P., Sanyal, A.J., Eds.; Saunders-Elsevier Inc.: Philadelphia, PA, USA, 2012; pp. 142-156.e4.
20. Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: The next generation. Cell 2011, 144, 646-674.
21. Ishibashi, H.; Nakamura, M.; Komori, A.; Migita, K.; Shimoda, S. Liver architecture, cell function, and disease. Semin. Immunopathol. 2009, 31, 399-409.
22. Michalopoulos, G.K. Liver regeneration after partial hepatectomy: Critical analysis of mechanistic dilemmas. Am. J. Pathol. 2010, 176, 2-13.
23. Michalopoulos, G.K. Liver regeneration. J. Cell. Physiol. 2007, 213, 286-300.
24. Mitchell, C.; Willenbring, H. A reproducible and well-tolerated method for 2/3 partial hepatectomy in mice. Nat. Protoc. 2008, 3, 1167-1170.
25. Roncalli, M.; Park, Y.N.; di Tommaso, L. Histopathological classification of hepatocellular carcinoma. Dig. Liver Dis. 2010, 42, S228-S234.
26. Okuda, K. Hepatocellular carcinoma. J. Hepatol. 2000, 32, 225-237.
27. Asia-Pacific Working Party on Prevention of Hepatocellular Carcinoma Prevention of hepatocellular carcinoma in the Asia-Pacific region: Consensus statements. J. Gastroenterol. Hepatol. 2010, 25, 657-663.
28. Bruix, J.; Sherman, M.; Llovet, J.M.; Beaugrand, M.; Lencioni, R.; Burroughs, A.K.; Christensen, E.; Pagliaro, L.; Colombo, M.; Rodés, J. EASL Panel of Experts on HCC Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J. Hepatol. 2001, 35, 421-430.
29. European Association for the Study of the Liver. European Organisation for Research and Treatment of Cancer EASL-EORTC clinical practice guidelines: Management of hepatocellular carcinoma. J. Hepatol. 2012, 56, 908-943.
30. Marrero, J.A.; Fontana, R.J.; Barrat, A.; Askari, F.; Conjeevaram, H.S.; Su, G.L.; Lok, A.S. Prognosis of hepatocellular carcinoma: Comparison of 7 staging systems in an American cohort. Hepatology 2005, 41, 707-716.
31. Varela, M.; Bruix, J. Hepatocellular carcinoma in the United States. Lessons from a population-based study in Medicare recipients. J. Hepatol. 2006, 44, 8-10.
32. Beyoǧlu, D.; Imbeaud, S.; Maurhofer, O.; Bioulac-Sage, P.; Zucman Rossi, J.; Dufour, J.-F.; Idle, J.R. Tissue metabolomics of hepatocellular carcinoma: Tumor energy metabolism and the role of transcriptomic classification. Hepatology 2013, 58, 229-238.
33. Lee, J.S.; Thorgeirsson, S.S. Comparative and integrative functional genomics of HCC. Oncogene 2006, 25, 3801-3809.
34. Pei, Y.; Zhang, T.; Renault, V.; Zhang, X. An overview of hepatocellular carcinoma study by omics-based methods. Acta Biochim. Biophys. Sin. 2009, 41, 1-15.
35. Uehara, T.; Ainslie, G.R.; Kutanzi, K.; Pogribny, I.P.; Muskhelishvili, L.; Izawa, T.; Yamate, J.; Kosyk, O.; Shymonyak, S.; Bradford, B.U.; et al. Molecular mechanisms of fibrosis-associated promotion of liver carcinogenesis. Toxicol. Sci. 2013, 132, 53-63.
36. Borzio, M.; Bruno, S.; Roncalli, M.; Mels, G.C.; Ramella, G.; Borzio, F.; Leandro, G.; Servida, E.; Podda, M. Liver cell dysplasia is a major risk factor for hepatocellular carcinoma in cirrhosis: A prospective study. Gastroenterology 1995, 108, 812-817.
37. Nishida, N.; Goel, A. Genetic and epigenetic signatures in human hepatocellular carcinoma: A systematic review. Curr. Genomics 2011, 12, 130.
38. Arzumanyan, A.; Reis, H.M.G.P.V.; Feitelson, M.A. Pathogenic mechanisms in HBV-and HCV-associated hepatocellularcarcinoma. Nat. Rev. Cancer 2013, 13, 123-135.
39. Breuhahn, K.; Longerich, T.; Schirmacher, P. Dysregulation of growth factor signaling in human hepatocellular carcinoma. Oncogene 2006, 25, 3787-3800.
40. Van Malenstein, H.; van Pelt, J.; Verslype, C. Molecular classification of hepatocellular carcinoma anno 2011. Eur. J. Cancer 2011, 47, 1789-1797.
41. Zucman-Rossi, J.; Benhamouche, S.; Godard, C.; Boyault, S.; Grimber, G.; Balabaud, C.; Cunha, A.S.; Bioulac-Sage, P.; Perret, C. Differential effects of inactivated Axin1 and activated beta-catenin mutations in human hepatocellular carcinomas. Oncogene 2007, 26, 774-780.
42. Micsenyi, A.; Tan, X.; Sneddon, T.; Luo, J.-H.; Michalopoulos, G.K.; Monga, S.P. β-Catenin is temporally regulated during normal liver development. Gastroenterology 2004, 126, 1134-1146.
43. Monga, S.P.; Pediaditakis, P.; Mule, K.; Stolz, D.B.; Michalopoulos, G.K. Changes in WNT/beta-catenin pathway during regulated growth in rat liver regeneration. Hepatology 2001, 33, 1098-1109.
44. Pez, F.; Lopez, A.; Kim, M.; Wands, J.R.; Caron de Fromentel, C.; Merle, P. Wnt signaling and hepatocarcinogenesis: Molecular targets for the development of innovative anticancer drugs. J. Hepatol. 2013, 59, 1107-1117.
45. Edamoto, Y.; Hara, A.; Biernat, W.; Terracciano, L.; Cathomas, G.; Riehle, H.-M.; Matsuda, M.; Fujii, H.; Scoazec, J.-Y.; Ohgaki, H. Alterations of RB1, p53 and Wnt pathways in hepatocellular carcinomas associated with hepatitis C, hepatitis B and alcoholic liver cirrhosis. Int. J. Cancer 2003, 106, 334-341.
46. Austinat, M.; Dunsch, R.; Wittekind, C.; Tannapfel, A.; Gebhardt, R.; Gaunitz, F. Correlation between beta-catenin mutations and expression of Wnt-signaling target genes in hepatocellular carcinoma. Mol. Cancer 2008, 7, 21.
47. Schlaeger, C.; Longerich, T.; Schiller, C.; Bewerunge, P.; Mehrabi, A.; Toedt, G.; Kleeff, J.; Ehemann, V.; Eils, R.; Lichter, P.; et al. Etiology-dependent molecular mechanisms in human hepatocarcinogenesis. Hepatology 2008, 47, 511-520.
48. Yuen, M.F.; Wu, P.C.; Lai, V.C.; Lau, J.Y.; Lai, C.L. Expression of c-Myc, c-Fos, and c-jun in hepatocellular carcinoma. Cancer 2001, 91, 106-112.
49. Chan, K.-L.; Guan, X.-Y.; Ng, I.O.-L. High-throughput tissue microarray analysis of c-myc activation in chronic liver diseases and hepatocellular carcinoma. Hum. Pathol. 2004, 35, 1324-1331.
50. Shachaf, C.M.; Kopelman, A.M.; Arvanitis, C.; Karlsson, A.; Beer, S.; Mandl, S.; Bachmann, M.H.; Borowsky, A.D.; Ruebner, B.; Cardiff, R.D.; et al. MYC inactivation uncovers pluripotent differentiation and tumour dormancy in hepatocellular cancer. Nature 2004, 431, 1112-1117.
51. Lin, C.-P.; Liu, C.-R.; Lee, C.-N.; Chan, T.-S.; Liu, H.E. Targeting c-Myc as a novel approach for hepatocellular carcinoma. World J. Hepatol. 2010, 2, 16-20.
52. Osada, S.; Kanematsu, M.; Imai, H.; Goshima, S.; Sugiyama, Y. Evaluation of extracellular signal regulated kinase expression and its relation to treatment of hepatocellular carcinoma. J. Am. Coll. Surg. 2005, 201, 405-411.
53. Christensen, J.G.; Burrows, J.; Salgia, R. c-Met as a target for human cancer and characterization of inhibitors for therapeutic intervention. Cancer Lett. 2005, 225, 1-26.
54. Malumbres, M.; Harlow, E.; Hunt, T.; Hunter, T.; Lahti, J.M.; Manning, G.; Morgan, D.O.; Tsai, L.-H.; Wolgemuth, D.J. Cyclin-dependent kinases: A family portrait. Nat. Cell Biol. 2009, 11, 1275-1276.
55. Gopinathan, L.; Ratnacaram, C.K.; Kaldis, P. Established and novel Cdk/cyclin complexes regulating the cell cycle and development. Results Probl. Cell Differ. 2011, 53, 365-389.
56. Ortega, S.; Malumbres, M.; Barbacid, M. Cyclin D-dependent kinases, INK4 inhibitors and cancer. Biochim. Biophys. Acta 2002, 1602, 73-87.
57. Albrecht, J.H.; Poon, R.Y.; Ahonen, C.L.; Rieland, B.M.; Deng, C.; Crary, G.S. Involvement of p21 and p27 in the regulation of CDK activity and cell cycle progression in the regenerating liver. Oncogene 1998, 16, 2141-2150.
58. Pujol, M.J.; Jaime, M.; Serratosa, J.; Jaumot, M.; Agell, N.; Bachs, O. Differential association of p21Cip1 and p27Kip1 with cyclin E-CDK2 during rat liver regeneration. J. Hepatol. 2000, 33, 266-274.
59. Ilyin, G.P.; Glaise, D.; Gilot, D.; Baffet, G.; Guguen-Guillouzo, C. Regulation and role of p21 and p27 cyclin-dependent kinase inhibitors during hepatocyte differentiation and growth. Am. J. Physiol. Gastrointest. Liver Physiol. 2003, 285, G115-G127.
60. Kurinna, S.; Barton, M.C. Cascades of transcription regulation during liver regeneration. Int. J. Biochem. Cell Biol. 2011, 43, 189-197.
61. Rickheim, D.G.; Nelsen, C.J.; Fassett, J.T.; Timchenko, N.A.; Hansen, L.K.; Albrecht, J.H. Differential regulation of cyclins D1 and D3 in hepatocyte proliferation. Hepatology 2002, 36, 30-38.
62. Albrecht, J.H.; Hu, M.Y.; Cerra, F.B. Distinct patterns of cyclin D1 regulation in models of liver regeneration and human liver. Biochem. Biophys. Res. Commun. 1995, 209, 648-655.
63. Albrecht, J.H.; Hansen, L.K. Cyclin D1 promotes mitogen-independent cell cycle progression in hepatocytes. Cell Growth Differ. 1999, 10, 397.
64. Loyer, P.; Cariou, S.; Glaise, D.; Bilodeau, M.; Baffet, G.; Guguen-Guillouzo, C. Growth factor dependence of progression through G and S phases of adult rat hepatocytes in vitro. J. Biol. Chem. 1996, 271, 11484-11492.
65. Boylan, J.M.; Gruppuso, P.A. D-type cyclins and G1 progression during liver development in the rat. Biochem. Biophys. Res. Commun. 2005, 330, 722-730.
66. Kato, J.; Matsuoka, M.; Strom, D. Regulation of cyclin D-dependent kinase 4 (cdk4) by cdk4-activating kinase. Mol. Cell. Biol. 1994, 14, 2713-2721.
67. Jaumot, M.; Estanyol, J.M.; Serratosa, J.; Agell, N.; Bachs, O. Activation of cdk4 and cdk2 during rat liver regeneration is associated with intranuclear rearrangements of cyclin-cdk complexes. Hepatology 1999, 29, 385-395.
68. Bisteau, X.; Paternot, S.; Colleoni, B.; Ecker, K.; Coulonval, K.; de Groote, P.; Declercq, W.; Hengst, L.; Roger, P.P. CDK4 T172 phosphorylation is central in a CDK7-dependent bidirectional CDK4/CDK2 interplay mediated by p21 phosphorylation at the restriction point. PLoS Genet. 2013, 9, e1003546.
69. Henley, S.A.; Dick, F.A. The retinoblastoma family of proteins and their regulatory functions in the mammalian cell division cycle. Cell Div. 2012, 7, 10.
70. Dick, F.A. Structure-function analysis of the retinoblastoma tumor suppressor protein-Is the whole a sum of its parts? Cell Div. 2007, 2, 26.
71. Rubin, S.M. Deciphering the retinoblastoma protein phosphorylation code. Trends Biochem. Sci. 2013, 38, 12-19.
72. Lundberg, A.S.; Weinberg, R.A. Functional inactivation of the retinoblastoma protein requires sequential modification by at least two distinct cyclin-cdk complexes. Mol. Cell. Biol. 1998, 18, 753-761.
73. Ezhevsky, S.A.; Nagahara, H.; Vocero-Akbani, A.M.; Gius, D.R.; Wei, M.C.; Dowdy, S.F. Hypo-phosphorylation of the retinoblastoma protein (pRb) by cyclin D: Cdk4/6 complexes results in active pRb. Proc. Natl. Acad. Sci. USA 1997, 94, 10699-10704.
74. Yao, G.; Lee, T.J.; Mori, S.; Nevins, J.R.; You, L. A bistable Rb-E2F switch underlies the restriction point. Nat. Cell Biol. 2008, 10, 476-482.
75. Albrecht, J.H.; Meyer, A.H.; Hu, M.Y. Regulation of cyclin-dependent kinase inhibitor p21WAF1/Cip1/Sdi1 gene expression in hepatic regeneration. Hepatology 1997, 25, 557-563.
76. LaBaer, J.; Garrett, M.D.; Stevenson, L.F.; Slingerland, J.M.; Sandhu, C.; Chou, H.S.; Fattaey, A.; Harlow, E. New functional activities for the p21 family of CDK inhibitors. Genes Dev. 1997, 11, 847-862.
77. Zhang, H.; Hannon, G.J.; Beach, D. p21-containing cyclin kinases exist in both active and inactive states. Genes Dev. 1994, 8, 1750-1758.
78. Cheng, M.; Olivier, P.; Diehl, J.; Fero, M. The p21Cip1 and p27Kip1 CDK -inhibitors{norm of matrix} are essential activators of cyclin D-dependent kinases in murine fibroblasts. EMBO J. 1999, 18, 1571-1583.
79. Sherr, C.J.; Roberts, J.M. CDK inhibitors: Positive and negative regulators of G1-phase progression. Genes Dev. 1999, 13, 1501-1512.
80. Zhu, H.; Nie, L.; Maki, C.G. Cdk2-dependent Inhibition of p21 stability via a C-terminal cyclin-binding motif. J. Biol. Chem. 2005, 280, 29282-29288.
81. Hayashi, E.; Yasui, A.; Oda, K.; Nagino, M.; Nimura, Y.; Nakanishi, M.; Motoyama, N.; Ikeda, K.; Matsuura, A. Loss of p27Kip1 accelerates DNA replication after partial hepatectomy in mice. J. Surg. Res. 2003, 111, 196-202.
82. Lu, Z.; Hunter, T. Ubiquitylation and proteasomal degradation of the p21Cip1, p27Kip1 and p57Kip2 CDK inhibitors. Cell Cycle 2010, 9, 2342-2352.
83. Starostina, N.G.; Kipreos, E.T. Multiple degradation pathways regulate versatile CIP/KIP CDK inhibitors. Trends Cell Biol. 2012, 22, 33-41.
84. Welcker, M.; Singer, J.; Loeb, K.R.; Grim, J.; Bloecher, A.; Gurien-West, M.; Clurman, B.E.; Roberts, J.M. Multisite phosphorylation by Cdk2 and GSK3 controls cyclin E degradation. Mol. Cell 2003, 12, 381-392.
85. Hao, B.; Oehlmann, S.; Sowa, M.E.; Harper, J.W.; Pavletich, N.P. Structure of a Fbw7-Skp1-cyclin E complex: Multisite-phosphorylated substrate recognition by SCF ubiquitin ligases. Mol. Cell 2007, 26, 131-143.
86. Merrick, K.A.; Larochelle, S.; Zhang, C.; Allen, J.J.; Shokat, K.M.; Fisher, R.P. Distinct activation pathways confer cyclin-binding specificity on Cdk1 and Cdk2 in human cells. Mol. Cell 2008, 32, 662-672.
87. Zhang, X.; Xu, H.J.; Murakami, Y.; Sachse, R.; Yashima, K.; Hirohashi, S.; Hu, S.X.; Benedict, W.F.; Sekiya, T. Deletions of chromosome 13q, mutations in Retinoblastoma 1, and retinoblastoma protein state in human hepatocellular carcinoma. Cancer Res. 1994, 54, 4177-4182.
88. Nakamura, T.; Iwamura, Y.; Kaneko, M.; Nakagawa, K.; Kawai, K.; Mitamura, K.; Futagawa, T.; Hayashi, H. Deletions and rearrangements of the retinoblastoma gene in hepatocellular carcinoma, insulinoma and some neurogenic tumors as found in a study of 121 tumors. Jpn. J. Clin. Oncol. 1991, 21, 325-329.
89. Murakami, Y.; Hayashi, K.; Hirohashi, S.; Sekiya, T. Aberrations of the tumor suppressor p53 and retinoblastoma genes in human hepatocellular carcinomas. Cancer Res. 1991, 51, 5520-5525.
90. Seki, S.; Kawakita, N.; Yanai, A.; Kitada, T.; Sakai, Y.; Nakatani, K.; Yamada, T.; Sakaguchi, H.; Kuroki, T. Expression of the retinoblastoma gene product in human hepatocellular carcinoma. Hum. Pathol. 1995, 26, 366-374.
91. Liew, C.T.; Li, H.-M.; Lo, K.-W.; Leow, C.K.; Chan, J.Y.; Hin, L.Y.; Lau, W.Y.; Lai, P.B.; Lim, B.K.; Huang, J. High frequency of p16INK4A gene alterations in hepatocellular carcinoma. Oncogene 1999, 18, 789-795.
92. Suh, S.I.; Pyun, H.Y.; Cho, J.W.; Baek, W.K.; Park, J.B.; Kwon, T.; Park, J.W.; Suh, M.H.; Carson, D.A. 5-Aza-2'-deoxycytidine leads to down-regulation of aberrant p16INK4A RNA transcripts and restores the functional retinoblastoma protein pathway in hepatocellular carcinoma cell lines. Cancer Lett. 2000, 160, 81-88.
93. Herman, J.G.; Merlo, A.; Mao, L.I.; Lapidus, R.G.; Issa, J. Inactivation of the CDKN2/p16/MTS1 gene is frequently associated with aberrant DNA methylation in all common human cancers. Cancer Res. 1995, 55, 4525-4530.
94. Chaubert, P.; Gayer, R.; Zimmermann, A.; Fontolliet, C.; Stamm, B.; Bosman, F.; Shaw, P. Germ-line mutations of the p16INK4/MTS1 gene occur in a subset of patients with hepatocellular carcinoma. Hepatology 1997, 25, 1376-1381.
95. Biden, K.; Young, J.; Buttenshaw, R.; Searle, J.; Cooksley, G.; Xu, D.B.; Leggett, B. Frequency of mutation and deletion of the tumor suppressor gene CDKN2A (MTS1/p16) in hepatocellular carcinoma from an Australian population. Hepatology 1997, 25, 593-597.
96. Zhu, Y.-Z.; Zhu, R.; Shi, L.-G.; Mao, Y.; Zheng, G.-J.; Chen, Q.; Zhu, H.-G. Hepatitis B virus X protein promotes hypermethylation of p16INK4A promoter through upregulation of DNA methyltransferases in hepatocarcinogenesis. Exp. Mol. Path. 2010, 89, 268-275.
97. Zhu, Y.Z.; Zhu, R.; Fan, J.; Pan, Q.; Li, H.; Chen, Q.; Zhu, H.G. Hepatitis B virus X protein induces hypermethylation of p16INK4A promoter via DNA methyltransferases in the early stage of HBV-associated hepatocarcinogenesis. J. Viral Hepat. 2010, 17, 98-107.
98. Kaneto, H.; Sasaki, S.; Yamamoto, H.; Itoh, F.; Toyota, M.; Suzuki, H.; Ozeki, I.; Iwata, N.; Ohmura, T.; Satoh, T. Detection of hypermethylation of thep16INK4A gene promoter in chronic hepatitis and cirrhosis associated with hepatitis B or C virus. Gut 2001, 48, 372-377.
99. Shim, Y.-H.; Yoon, G.-S.; Choi, H.-J.; Chung, Y.H.; Yu, E. p16 Hypermethylation in the early stage of hepatitis B virus-associated hepatocarcinogenesis. Cancer Lett. 2003, 190, 213-219.
100. Li, X.; Hui, A.-M.; Sun, L.; Hasegawa, K.; Torzilli, G.; Minagawa, M.; Takayama, T.; Makuuchi, M. p16INK4A hypermethylation is associated with hepatitis virus infection, age, and gender in hepatocellular carcinoma. Clin. Cancer Res. 2004, 10, 7484-7489.
101. Zhu, R.; Li, B.-Z.; Li, H.; Ling, Y.-Q.; Hu, X.-Q.; Zhai, W.-R.; Zhu, H.-G. Association of p16INK4A hypermethylation with hepatitis B virus X protein expression in the early stage of HBV-associated hepatocarcinogenesis. Pathol. Int. 2007, 57, 328-336.
102. Munakata, T.; Liang, Y.; Kim, S.; McGivern, D.R.; Huibregtse, J.; Nomoto, A.; Lemon, S.M. Hepatitis C virus induces E6AP-dependent degradation of the retinoblastoma protein. PLoS Pathog. 2007, 3, e139.
103. Munakata, T.; Nakamura, M.; Liang, Y.; Li, K.; Lemon, S.M. Down-regulation of the retinoblastoma tumor suppressor by the hepatitis C virus NS5B RNA-dependent RNA polymerase. Proc. Natl. Acad. Sci. USA 2005, 102, 18159-18164.
104. Higashitsuji, H.; Itoh, K.; Nagao, T.; Dawson, S.; Nonoguchi, K.; Kido, T.; Mayer, R. J.; Arii, S.; Fujita, J. Reduced stability of retinoblastoma protein by gankyrin, an oncogenic ankyrin-repeat protein overexpressed in hepatomas. Nat. Med. 2000, 6, 96-99.
105. Tan, L.; Fu, X.-Y.; Liu, S.-Q.; Li, H.-H.; Hong, Y.; Wu, M.-C.; Wang, H.-Y. Expression of p28GANK and its correlation with RB in human hepatocellular carcinoma. Liver Int. 2005, 25, 667-676.
106. Fu, J.; Chen, Y.; Cao, J.; Luo, T.; Qian, Y.-W.; Yang, W.; Ren, Y.-B.; Su, B.; Cao, G.-W.; Yang, Y.; et al. p28GANK overexpression accelerates hepatocellular carcinoma invasiveness and metastasis via phosphoinositol 3-kinase/AKT/hypoxia-inducible factor-1α pathways. Hepatology 2010, 53, 181-192.
107. Chen, Y.; Li, H.H.; Fu, J.; Wang, X.F.; Ren, Y.-B.; Dong, L.-W.; Tang, S.H.; Liu, S.Q.; Wu, M.C.; Wang, H.-Y. Oncoprotein p28GANK binds to RelA and retains NF-κB in the cytoplasm through nuclear export. Cell Res. 2007, 17, 1020-1029.
108. Dong, L.-W.; Yang, G.-Z.; Pan, Y.-F.; Chen, Y.; Tan, Y.-X.; Dai, R.-Y.; Ren, Y.-B.; Fu, J.; Wang, H.-Y. The oncoprotein p28. Cell Res. 2011, 21, 1248-1261.
109. Liu, Y.; Higashitsuji, H.; Higashitsuji, H.; Itoh, K.; Sakurai, T.; Koike, K.; Hirota, K.; Fukumoto, M.; Fujita, J. Overexpression of gankyrin in mouse hepatocytes induces hemangioma by suppressing factor inhibiting hypoxia-inducible factor-1 (FIH-1) and activating hypoxia-inducible factor-1. Biochem. Biophys. Res. Commun. 2013, 432, 22-27.
110. Higashitsuji, H.; Higashitsuji, H.; Itoh, K.; Sakurai, T.; Nagao, T.; Sumitomo, Y.; Sumitomo, H.; Masuda, T.; Dawson, S.; Shimada, Y.; et al. The oncoprotein gankyrin binds to MDM2/HDM2, enhancing ubiquitylation and degradation of p53. Cancer Cell 2005, 8, 75-87.
111. Dawson, S.; Higashitsuji, H.; Wilkinson, A.J.; Fujita, J.; Mayer, R.J. Gankyrin: A new oncoprotein and regulator of pRb and p53. Trends Cell Biol. 2006, 16, 229-233.
112. Qiu, W.; Wu, J.; Walsh, E.M.; Zhang, Y.; Chen, C.-Y.; Fujita, J.; Xiao, Z.-X.J. Retinoblastoma protein modulates gankyrin-MDM2 in regulation of p53 stability and chemosensitivity in cancer cells. Oncogene 2008, 27, 4034-4043.
113. Morel, A.P.; Unsal, K.; Cagatay, T.; Ponchel, F.; Carr, B.; Ozturk, M. p53 but not p16INK4a induces growth arrest in retinoblastoma-deficient hepatocellular carcinoma cells. J. Hepatol. 2000, 33, 254-265.
114. Hui, A.M.; Li, X.; Makuuchi, M.; Takayama, T.; Kubota, K. Over-expression and lack of retinoblastoma protein are associated with tumor progression and metastasis in hepatocellular carcinoma. Int. J. Cancer 1999, 84, 604-608.
115. Hui, A.-M.; Shi, Y.-Z.; Li, X.; Takayama, T.; Makuuchi, M. Loss of p16INK4 protein, alone and together with loss of retinoblastoma protein, correlate with hepatocellular carcinoma progression. Cancer Lett. 2000, 154, 93-99.
116. Mayhew, C.N.; Bosco, E.E.; Fox, S.R.; Okaya, T.; Tarapore, P.; Schwemberger, S.J.; Babcock, G.F.; Lentsch, A.B.; Fukasawa, K.; Knudsen, E.S. Liver-specific pRB loss results in ectopic cell cycle entry and aberrant ploidy. Cancer Res. 2005, 65, 4568-4577.
117. Viatour, P.; Ehmer, U.; Saddic, L.A.; Dorrell, C.; Andersen, J.B.; Lin, C.; Zmoos, A.-F.; Mazur, P.K.; Schaffer, B.E.; Ostermeier, A.; et al. Notch signaling inhibits hepatocellular carcinoma following inactivation of the RB pathway. J. Exp. Med. 2011, 208, 1963-1976.
118. Mayhew, C.N.; Carter, S.L.; Fox, S.R.; Sexton, C.R.; Reed, C.A.; Srinivasan, S.V.; Liu, X.; Wikenheiser Brokamp, K.; Boivin, G.P.; Lee, J.-S.; et al. RB loss abrogates cell cycle control and genome integrity to promote liver tumorigenesis. Gastroenterology 2007, 133, 976-984.
119. Reed, C.A.; Mayhew, C.N.; McClendon, A.K.; Yang, X.; Witkiewicz, A.; Knudsen, E.S. RB has a critical role in mediating the in vivo checkpoint response, mitigating secondary DNA damage and suppressing liver tumorigenesis initiated by aflatoxin B1. Oncogene 2009, 28, 4434-4443.
120. McClendon, A.K.; Dean, J.L.; Ertel, A.; Fu, Z.; Rivadeneira, D.B.; Reed, C.A.; Bourgo, R.J.; Witkiewicz, A.; Addya, S.; Mayhew, C.N.; et al. RB and p53 cooperate to prevent liver tumorigenesis in response to tissue damage. Gastroenterology 2011, 141, 1439-1450.
121. Zhao, H.; Bauzon, F.; Fu, H.; Lu, Z.; Cui, J.; Nakayama, K.; Nakayama, K.I.; Locker, J.; Zhu, L. Skp2 deletion unmasks a p27 safeguard that blocks tumorigenesis in the absence of pRb and p53 tumor suppressors. Cancer Cell 2013, 24, 645-659.
122. Zhang, Y.J.; Jiang, W.; Chen, C.J.; Lee, C.S.; Kahn, S.M.; Santella, R.M.; Weinstein, I.B. Amplification and overexpression of cyclin D1 in human hepatocellular carcinoma. Biochem. Biophys. Res. Commun. 1993, 196, 1010-1016.
123. Nishida, N.; Fukuda, Y.; Komeda, T.; Kita, R.; Sando, T.; Furukawa, M.; Amenomori, M.; Shibagaki, I.; Nakao, K.; Ikenaga, M. Amplification and overexpression of the cyclin D1 gene in aggressive human hepatocellular carcinoma. Cancer Res. 1994, 54, 3107-3110.
124. Wang, K.; Lim, H.Y.; Shi, S.; Lee, J.; Deng, S.; Xie, T.; Zhu, Z.; Wang, Y.; Pocalyko, D.; Yang, W.J.; et al. Genomic landscape of copy number aberrations enables the identification of oncogenic drivers in hepatocellular carcinoma. Hepatology 2013, 58, 706-717.
125. Sawey, E.T.; Chanrion, M.; Cai, C.; Wu, G.; Zhang, J.; Zender, L.; Zhao, A.; Busuttil, R.W.; Yee, H.; Stein, L.; et al. Identification of a therapeutic strategy targeting amplified FGF19 in liver cancer by oncogenomic screening. Cancer Cell 2011, 19, 347-358.
126. Woo, H.G.; Park, E.S.; Thorgeirsson, S.S.; Kim, Y.J. Exploring genomic profiles of hepatocellular carcinoma. Mol. Carcinog. 2011, 50, 235-243.
127. Joo, M.; Kang, Y.K.; Kim, M.R.; Lee, H.K.; Jang, J.J. Cyclin D1 overexpression in hepatocellular carcinoma. Liver 2001, 21, 89-95.
128. Choi, Y.J.; Anders, L. Signaling through cyclin D-dependent kinases. Oncogene 2013, in press.
129. Klein, E.A.; Assoian, R.K. Transcriptional regulation of the cyclin D1 gene at a glance. J. Cell Sci. 2008, 121, 3853-3857.
130. Diehl, J.A.; Cheng, M.; Roussel, M.F.; Sherr, C.J. Glycogen synthase kinase-3beta regulates cyclin D1 proteolysis and subcellular localization. Genes Dev. 1998, 12, 3499-3511.
131. Musgrove, E.A.; Caldon, C.E.; Barraclough, J.; Stone, A.; Sutherland, R.L. Cyclin D as a therapeutic target in cancer. Nat. Rev. Cancer 2011, 11, 558-572.
132. Tetsu, O.; McCormick, F. Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature 1999, 398, 422-426.
133. Shtutman, M.; Zhurinsky, J.; Simcha, I.; Albanese, C.; D'Amico, M.; Pestell, R.; Ben-Ze'ev, A. The cyclin D1 gene is a target of the beta-catenin/LEF-1 pathway. Proc. Natl. Acad. Sci. USA 1999, 96, 5522-5527.
134. Cui, J.; Zhou, X.; Liu, Y.; Tang, Z.; Romeih, M. Wnt signaling in hepatocellular carcinoma: Analysis of mutation and expression of beta-catenin, T-cell factor-4 and glycogen synthase kinase 3-beta genes. J. Gastroenterol. Hepatol. 2003, 18, 280-287.
135. Joo, M.; Lee, H.K.; Kang, Y.K. Expression of beta-catenin in hepatocellular carcinoma in relation to tumor cell proliferation and cyclin D1 expression. J. Korean Med. Sci. 2003, 18, 211-217.
136. Patil, M.A.; Lee, S.A.; Macias, E.; Lam, E.T.; Xu, C.; Jones, K.D.; Ho, C.; Rodriguez-Puebla, M.; Chen, X. Role of cyclin D1 as a mediator of c-Met- and beta-catenin-induced hepatocarcinogenesis. Cancer Res. 2009, 69, 253-261.
137. Nejak-Bowen, K.N.; Thompson, M.D.; Singh, S.; Bowen, W.C.; Dar, M.J.; Khillan, J.; Dai, C.; Monga, S.P. Accelerated liver regeneration and hepatocarcinogenesis in mice overexpressing serine-45 mutant β-catenin. Hepatology 2010, 51, 1603-1613.
138. Luo, D.; Liu, Q.-F.; Gove, C.; Naomov, N.V.; Su, J.-J.; Williams, R. Analysis of N-ras gene mutation and p53 gene expression in human hepatocellular carcinomas. World J. Gastroenterol. 1998, 4, 97-99.
139. Newell, P.; Toffanin, S.; Villanueva, A.; Chiang, D.Y.; Minguez, B.; Cabellos, L.; Savic, R.; Hoshida, Y.; Lim, K.H.; Melgar-Lesmes, P.; et al. Ras pathway activation in hepatocellular carcinoma and anti-tumoral effect of combined sorafenib and rapamycin in vivo. J. Hepatol. 2009, 51, 725-733.
140. Colombino, M.; Sperlongano, P.; Izzo, F.; Tatangelo, F.; Botti, G.; Lombardi, A.; Accardo, M.; Tarantino, L.; Sordelli, I.; Agresti, M.; et al. BRAF and PIK3CA genes are somatically mutated in hepatocellular carcinoma among patients from South Italy. Cell Death Dis. 2012, 3, e259.
141. Calvisi, D.F.; Ladu, S.; Gorden, A.; Farina, M.; Conner, E.A.; Lee, J.-S.; Factor, V.M.; Thorgeirsson, S.S. Ubiquitous activation of Ras and Jak/Stat pathways in human HCC. Gastroenterology 2006, 130, 1117-1128.
142. Ito, Y.; Sasaki, Y.; Horimoto, M.; Wada, S.; Tanaka, Y.; Kasahara, A.; Ueki, T.; Hirano, T.; Yamamoto, H.; Fujimoto, J.; et al. Activation of mitogen-activated protein kinases/extracellular signal-regulated kinases in human hepatocellular carcinoma. Hepatology 1998, 27, 951-958.
143. Huynh, H.; Do, P.T.; Nguyen, T.H.; Chow, P.; Tan, P.H.; Quach, T.H.; Van, T.; Soo, K.C.; Tran, E. Extracellular signal-regulated kinase induces cyclin D1 and Cdk-2 expression and phosphorylation of retinoblastoma in hepatocellular carcinoma. Int. J. Oncol. 2004, 25, 1839-1847.
144. Parekh, P.; Rao, K. Overexpression of cyclin D1 is associated with elevated levels of MAP kinases, Akt and Pak1 during diethylnitrosamine-induced progressive liver carcinogenesis. Cell Biol. Int. 2007, 31, 35-43.
145. Lau, C.K.; Yang, Z.F.; Lam, S.P.; Lam, C.T.; Ngai, P.; Tam, K.H.; Poon, R.T.-P.; Fan, S.-T. Inhibition of Stat3 activity by YC-1 enhances chemo-sensitivity in hepatocellular carcinoma. Cancer Biol. Ther. 2007, 6, 1900-1907.
146. Won, C.; Lee, C.S.; Lee, J.-K.; Kim, T.-J.; Lee, K.-H.; Yang, Y.M.; Kim, Y.-N.; Ye, S.-K.; Chung, M.-H. CADPE suppresses cyclin D1 expression in hepatocellular carcinoma by blocking IL-6-induced STAT3 activation. Anticancer Res. 2010, 30, 481-488.
147. Feng, D.Y.; Zheng, H.; Tan, Y.; Cheng, R.X. Effect of phosphorylation of MAPK and Stat3 and expression of c-fos and c-jun proteins on hepatocarcinogenesis and their clinical significance. World J. Gastroenterol. 2001, 7, 33-36.
148. Su, H.; Yang, J.-R.; Xu, T.; Huang, J.; Xu, L.; Yuan, Y.; Zhuang, S.-M. MicroRNA-101, down-regulated in hepatocellular carcinoma, promotes apoptosis and suppresses tumorigenicity. Cancer Res. 2009, 69, 1135-1142.
149. Murakami, Y.; Yasuda, T.; Saigo, K.; Urashima, T.; Toyoda, H.; Okanoue, T.; Shimotohno, K. Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissues. Oncogene 2006, 25, 2537-2545.
150. Xu, T.; Zhu, Y.; Xiong, Y.; Ge, Y.-Y.; Yun, J.-P.; Zhuang, S.-M. MicroRNA-195 suppresses tumorigenicity and regulates G1/S transition of human hepatocellular carcinoma cells. Hepatology 2009, 50, 113-121.
151. Zhang, W.; Kong, G.; Zhang, J.; Wang, T.; Ye, L.; Zhang, X. MicroRNA-520b inhibits growth of hepatoma cells by targeting MEKK2 and cyclin D1. PLoS One 2012, 7, e31450.
152. Park, S.G.; Chung, C.; Kang, H.; Kim, J.-Y.; Jung, G. Up-regulation of cyclin D1 by HBx is mediated by NF-kappaB2/BCL3 complex through kappaB site of cyclin D1 promoter. J. Biol. Chem. 2006, 281, 31770-31777.
153. Yamamoto, M.; Tamakawa, S.; Yoshie, M.; Yaginuma, Y.; Ogawa, K. Neoplastic hepatocyte growth associated with cyclin D1 redistribution from the cytoplasm to the nucleus in mouse hepatocarcinogenesis. Mol. Carcinog. 2006, 45, 901-913.
154. Diehl, J.A. Cycling to cancer with cyclin D1. Cancer Biol. Ther. 2002, 1, 226-231.
155. Sato, Y.; Itoh, F.; Hareyama, M.; Satoh, M.; Hinoda, Y.; Seto, M.; Ueda, R.; Imai, K. Association of cyclin D1 expression with factors correlated with tumor progression in human hepatocellular carcinoma. J. Gastroenterol. 1999, 34, 486-493.
156. Peng, S.Y.; Chou, S.P.; Hsu, H.C. Association of downregulation of cyclin D1 and of overexpression of cyclin E with p53 mutation, high tumor grade and poor prognosis in hepatocellular carcinoma. J. Hepatol. 1998, 29, 281-289.
157. Ito, Y.; Matsuura, N.; Sakon, M.; Miyoshi, E.; Noda, K.; Takeda, T.; Umeshita, K.; Nagano, H.; Nakamori, S.; Dono, K.; et al. Expression and prognostic roles of the G1-S modulators in hepatocellular carcinoma: p27 independently predicts the recurrence. Hepatology 1999, 30, 90-99.
158. Deane, N.G.; Parker, M.A.; Aramandla, R.; Diehl, L.; Lee, W.J.; Washington, M.K.; Nanney, L.B.; Shyr, Y.; Beauchamp, R.D. Hepatocellular carcinoma results from chronic cyclin D1 overexpression in transgenic mice. Cancer Res. 2001, 61, 5389-5395.
159. Rennstam, K.; Baldetorp, B.; Kytölä, S.; Tanner, M.; Isola, J. Chromosomal rearrangements and oncogene amplification precede aneuploidization in the genetic evolution of breast cancer. Cancer Res. 2001, 61, 1214-1219.
160. Ott, G.; Kalla, J.; Ott, M.M.; Schryen, B.; Katzenberger, T.; Müller, J.G.; Müller-Hermelink, H.K. Blastoid variants of mantle cell lymphoma: Frequent bcl-1 rearrangements at the major translocation cluster region and tetraploid chromosome clones. Blood 1997, 89, 1421-1429.
161. Nelsen, C.J.; Kuriyama, R.; Hirsch, B.; Negron, V.C.; Lingle, W.L.; Goggin, M.M.; Stanley, M.W.; Albrecht, J.H. Short term cyclin D1 overexpression induces centrosome amplification, mitotic spindle abnormalities, and aneuploidy. J. Biol. Chem. 2005, 280, 768-776.
162. Schraml, P.; Bucher, C.; Bissig, H.; Nocito, A.; Haas, P.; Wilber, K.; Seelig, S.; Kononen, J.; Mihatsch, M.J.; Dirnhofer, S.; et al. Cyclin E overexpression and amplification in human tumours. J. Pathol. 2003, 200, 375-382.
163. Jung, Y.J.; Lee, K.H.; Choi, D.W.; Han, C.J.; Jeong, S.H.; Kim, K.C.; Oh, J.W.; Park, T.K.; Kim, C.M. Reciprocal expressions of cyclin E and cyclin D1 in hepatocellular carcinoma. Cancer Lett. 2001, 168, 57-63.
164. Lv, Z.; Zhang, M.; Bi, J.; Xu, F.; Hu, S.; Wen, J. Promoter hypermethylation of a novel gene, ZHX2, in hepatocellular carcinoma. Am. J. Clin. Pathol. 2006, 125, 740-746.
165. Yue, X.; Zhang, Z.; Liang, X.; Gao, L.; Zhang, X.; Zhao, D.; Liu, X.; Ma, H.; Guo, M.; Spear, B.T.; et al. Zinc fingers and homeoboxes 2 inhibits hepatocellular carcinoma cell proliferation and represses expression of Cyclins A and E. Gastroenterology 2012, 142, 1559-1570.e2.
166. Tu, K.; Zheng, X.; Zan, X.; Han, S.; Yao, Y.; Liu, Q. Evaluation of Fbxw7 expression and its correlation with the expression of c-Myc, cyclin E and p53 in human hepatocellular carcinoma. Hepatol. Res. 2012, 42, 904-910.
167. Hagedorn, M.; Delugin, M.; Abraldes, I.; Allain, N.; Belaud-Rotureau, M.-A.; Turmo, M.; Prigent, C.; Loiseau, H.; Bikfalvi, A.; Javerzat, S. FBXW7/hCDC4 controls glioma cell proliferation in vitro and is a prognostic marker for survival in glioblastoma patients. Cell Div. 2007, 2, 9.
168. Akhoondi, S.; Sun, D.; von der Lehr, N.; Apostolidou, S.; Klotz, K.; Maljukova, A.; Cepeda, D.; Fiegl, H.; Dafou, D.; Dofou, D.; et al. FBXW7/hCDC4 is a general tumor suppressor in human cancer. Cancer Res. 2007, 67, 9006-9012.
169. Mao, J.-H.; Perez-losada, J.; Wu, D.; DelRosario, R.; Tsunematsu, R.; Nakayama, K.I.; Brown, K.; Bryson, S.; Balmain, A. Fbxw7/Cdc4 is a p53-dependent, haploinsufficient tumour suppressor gene. Nature 2004, 432, 775-779.
170. Welcker, M.; Clurman, B.E. FBW7 ubiquitin ligase: A tumour suppressor at the crossroads of cell division, growth and differentiation. Nat. Rev. Cancer 2008, 8, 83-93.
171. Tu, K.; Zheng, X.; Zhou, Z.; Li, C.; Zhang, J.; Gao, J.; Yao, Y. Recombinant human adenovirus-p53 injection induced apoptosis in hepatocellular carcinoma cell lines mediated by p53-Fbxw7 pathway, which controls c-Myc and cyclin E. PLoS One 2013, 8, e68574.
172. Li, K.; Lin, S.-Y.; Brunicardi, F.C.; Seu, P. Use of RNA interference to target cyclin E-overexpressing hepatocellular carcinoma. Cancer Res. 2003, 63, 3593-3597.
173. Pok, S.; Wen, V.; Shackel, N.; Alsop, A.; Pyakurel, P.; Fahrer, A.; Farrell, G.C.; Teoh, N.C. Cyclin E facilitates dysplastic hepatocytes to bypass G 1/S checkpoint in hepatocarcinogenesis. J. Gastroenterol. Hepatol. 2013, 28, 1545-1554.
174. Erdal, E.; Ozturk, N.; Cagatay, T.; Eksioglu-Demiralp, E.; Ozturk, M. Lithium-mediated downregulation of PKB/Akt and cyclin E with growth inhibition in hepatocellular carcinoma cells. Int. J. Cancer 2005, 115, 903-910.
175. Sayan, A.E.; Sayan, B.S.; Findikli, N.; Ozturk, M. Acquired expression of transcriptionally active p73 in hepatocellular carcinoma cells. Oncogene 2001, 20, 5111-5117.
176. Spruck, C.H.; Won, K.-A.; Reed, S.I. Deregulated cyclin E induces chromosome instability. Nature 1999, 401, 297-300.
177. Tane, S.; Chibazakura, T. Cyclin A overexpression induces chromosomal double-strand breaks in mammalian cells. Cell Cycle 2009, 8, 3900-3903.
178. Ekholm-Reed, S.; Méndez, J.; Tedesco, D.; Zetterberg, A.; Stillman, B.; Reed, S.I. Deregulation of cyclin E in human cells interferes with prereplication complex assembly. J. Cell Biol. 2004, 165, 789-800.
179. Chibazakura, T. Cyclin proteolysis and CDK inhibitors: Two redundant pathways to maintain genome stability in mammalian cells. Cell Cycle 2004, 3, 1243-1245.
180. Wheeler, L.W.; Lents, N.H.; Baldassare, J.J. Cyclin A-CDK activity during G1 phase impairs MCM chromatin loading and inhibits DNA synthesis in mammalian cells. Cell Cycle 2008, 7, 2179-2188.
181. Wang, J.; Chenivesse, X.; Henglein, B.; Bréchot, C. Hepatitis B virus integration in a cyclin A gene in a hepatocellular carcinoma. Nature 1990, 343, 555-557.
182. Chao, Y.; Shih, Y.-L.; Chiu, J.-H.; Chau, G.-Y.; Lui, W.-Y.; Yang, W.K.; Lee, S.-D.; Huang, T.-S. Overexpression of cyclin A but not Skp 2 correlates with the tumor relapse of human hepatocellular carcinoma. Cancer Res. 1998, 58, 985-990.
183. Bahnassy, A.A.; Zekri, A.-R.N.; Loutfy, S.A.; Mohamed, W.S.; Moneim, A.A.; Salem, S.E.; Sheta, M.M.; Omar, A.; Al-Zawahry, H. The role of cyclins and cyclin dependent kinases in development and progression of hepatitis C virus-genotype 4-associated hepatitis and hepatocellular carcinoma. Exp. Mol. Path. 2011, 91, 643-652.
184. Paterlini, P.; Flejou, J.-F.; de Mitri, M.S.; Pisi, E.; Franco, D.; Bréchot, C. Structure and expression of the cyclin A gene in human primary liver cancer. Correlation with flow cytometric parameters. J. Hepatol. 1995, 23, 47-52.
185. Nakajima, T.; Yasui, K.; Zen, K.; Inagaki, Y.; Fujii, H.; Minami, M.; Tanaka, S.; Taniwaki, M.; Itoh, Y.; Arii, S.; et al. Activation of B-Myb by E2F1 in hepatocellular carcinoma. Hepatol. Res. 2008, 38, 886-895.
186. Park, T.J.; Kim, J.-Y.; Oh, S.P.; Kang, S.Y.; Kim, B.W.; Wang, H.J.; Song, K.Y.; Kim, H.C.; Lim, I.K. TIS21 negatively regulates hepatocarcinogenesis by disruption of cyclin B1-Forkhead box M1 regulation loop. Hepatology 2008, 47, 1533-1543.
187. Hui, A.-M.; Kanai, Y.; Sakamoto, M.; Tsuda, H.; Hirohashi, S. Reduced p21WAF1/CIP1 expression and p53 mutation in hepatocellular carcinomas. Hepatology 1997, 25, 575-579.
188. Qin, L.F.; Ng, I.O. Expression of p27KIP1 and p21WAF1/CIP1 in primary hepatocellular carcinoma: Clinicopathologic correlation and survival analysis. Hum. Pathol. 2001, 32, 778-784.
189. Kao, J.-T.; Chuah, S.-K.; Huang, C.-C.; Chen, C.-L.; Wang, C.-C.; Hung, C.-H.; Chen, C.-H.; Wang, J.-H.; Lu, S.-N.; Lee, C.-M.; et al. p21WAF1 is an independent survival prognostic factor for patients with hepatocellular carcinoma after resection. Liver Int. 2007, 27, 772-781.
190. Tannapfel, A.; Grund, D.; Katalinic, A.; Uhlmann, D.; Köckerling, F.; Haugwitz, U.; Wasner, M.; Hauss, J.; Engeland, K.; Wittekind, C. Decreased expression of p27 protein is associated with advanced tumor stage in hepatocellular carcinoma. Int. J. Cancer 2000, 89, 350-355.
191. Hui, A.-M.; Sun, L.; Kanai, Y.; Sakamoto, M.; Hirohashi, S. Reduced p27Kip1 expression in hepatocellular carcinomas. Cancer Lett. 1998, 132, 67-73.
192. Fiorentino, M.; Altimari, A.; D'Errico, A.; Cukor, B.; Barozzi, C.; Loda, M.; Grigioni, W.F. Acquired expression of p27 is a favorable prognostic indicator in patients with hepatocellular carcinoma. Clin. Cancer Res. 2000, 6, 3966-3972.
193. Ray, R.B.; Steele, R.; Meyer, K.; Ray, R. Hepatitis C virus core protein represses p21WAF1/Cip1/Sid1 promoter activity. Gene 1998, 208, 331-336.
194. Jung, E.Y.; Lee, M.N.; Yang, H.Y.; Yu, D.; Jang, K.L. The repressive activity of hepatitis C virus core protein on the transcription of p21Waf1 is regulated by protein kinase A-mediated phosphorylation. Virus Res. 2001, 79, 109-115.
195. Otsuka, M.; Kato, N.; Lan, K.; Yoshida, H.; Kato, J.; Goto, T.; Shiratori, Y.; Omata, M. Hepatitis C virus core protein enhances p53 function through augmentation of DNA binding affinity and transcriptional ability. J. Biol. Chem. 2000, 275, 34122-34130.
196. Lu, W.; Lo, S.Y.; Chen, M.; Wu, K.J.; Fung, Y.K.; Ou, J.H. Activation of p53 tumor suppressor by hepatitis C virus core protein. Virology 1999, 264, 134-141.
197. Yamanaka, T.; Kodama, T.; Doi, T. Subcellular localization of HCV core protein regulates its ability for p53 activation and p21 suppression. Biochem. Biophys. Res. Commun. 2002, 294, 528-534.
198. Shiu, T.-Y.; Huang, S.-M.; Shih, Y.-L.; Chu, H.-C.; Chang, W.-K.; Hsieh, T.-Y. Hepatitis C virus core protein down-regulates p21Waf1/Cip1 and inhibits curcumin-induced apoptosis through microRNA-345 targeting in human hepatoma cells. PLoS One 2013, 8, e61089.
199. Nguyen, H.; Mudryj, M.; Guadalupe, M.; Dandekar, S. Hepatitis C virus core protein expression leads to biphasic regulation of the p21 cdk inhibitor and modulation of hepatocyte cell cycle. Virology 2003, 312, 245-253.
200. Qiao, L.; Leach, K.; McKinstry, R.; Gilfor, D.; Yacoub, A.; Park, J.S.; Grant, S.; Hylemon, P.B.; Fisher, P.B.; Dent, P. Hepatitis B virus X protein increases expression of p21Cip-1/WAF1/MDA6 and p27Kip-1 in primary mouse hepatocytes, leading to reduced cell cycle progression. Hepatology 2001, 34, 906-917.
201. waf1/cip1 and prolongs G1S transition via a p53-independent pathway in human hepatoma cells. Oncogene 2000, 19, 3384.
202. Yano, M.; Ohkoshi, S.; Aoki, Y.-H.; Takahashi, H.; Kurita, S.; Yamazaki, K.; Suzuki, K.; Yamagiwa, S.; Sanpei, A.; Fujimaki, S.; et al. Hepatitis B virus X induces cell proliferation in the hepatocarcinogenesis via up-regulation of cytoplasmic p21 expression. Liver Int. 2013, 33, 1218-1229.
203. Han, H.J.; Jung, E.Y.; Lee, W.J.; Jang, K.L. Cooperative repression of cyclin-dependent kinase inhibitor p21 gene expression by hepatitis B virus X protein and hepatitis C virus core protein. FEBS Lett. 2002, 518, 169-172.
204. Ahn, J.Y.; Chung, E.Y.; Kwun, H.J.; Jang, K.L. Transcriptional repression of p21Waf1 promoter by hepatitis B virus X protein via a p53-independent pathway. Gene 2001, 275, 163-168.
205. Hui, L.; Zatloukal, K.; Scheuch, H.; Stepniak, E.; Wagner, E.F. Proliferation of human HCC cells and chemically induced mouse liver cancers requires JNK1-dependent p21 downregulation. J. Clin. Invest. 2008, 118, 3943-3953.
206. Buitrago-Molina, L.E.; Marhenke, S.; Longerich, T.; Sharma, A.D.; Boukouris, A.E.; Geffers, R.; Guigas, B.; Manns, M.P.; Vogel, A. The degree of liver injury determines the role of p21 in liver regeneration and hepatocarcinogenesis in mice. Hepatology 2013, 58, 1143-1152.
207. Willenbring, H.; Sharma, A.D.; Vogel, A.; Lee, A.Y.; Rothfuss, A.; Wang, Z.; Finegold, M.; Grompe, M. Loss of p21 permits carcinogenesis from chronically damaged liver and kidney epithelial cells despite unchecked apoptosis. Cancer Cell 2008, 14, 59-67.
208. Fero, M.L.; Rivkin, M.; Tasch, M.; Porter, P.; Carow, C.E.; Firpo, E.; Polyak, K.; Tsai, L.H.; Broudy, V.; Perlmutter, R.M.; et al. A syndrome of multiorgan hyperplasia with features of gigantism, tumorigenesis, and female sterility in p27Kip1-deficient mice. Cell 1996, 85, 733-744.
209. Nakayama, K.; Ishida, N.; Shirane, M.; Inomata, A.; Inoue, T.; Shishido, N.; Horii, I.; Loh, D.Y.; Nakayama, K.-I. Mice lacking p27Kip1 display increased body size, multiple organ hyperplasia, retinal dysplasia, and pituitary tumors. Cell 1996, 85, 707-720.
210. Kiyokawa, H.; Kineman, R.D.; Manova-Todorova, K.O.; Soares, V.C.; Hoffman, E.S.; Ono, M.; Khanam, D.; Hayday, A.C.; Frohman, L.A.; Koff, A. Enhanced growth of mice lacking the Cyclin-dependent kinase inhibitor function of p27Kip1. Cell 1996, 85, 721-732.
211. Sun, D.; Ren, H.; Oertel, M.; Sellers, R.S.; Zhu, L. Loss of p27Kip1 enhances tumor progression in chronic hepatocyte injury-induced liver tumorigenesis with widely ranging effects on Cdk2 or Cdc2 activation. Carcinogenesis 2007, 28, 1859-1866.
212. Matsuda, Y.; Wakai, T.; Kubota, M.; Takamura, M.; Yamagiwa, S.; Aoyagi, Y.; Osawa, M.; Fujimaki, S.; Sanpei, A.; Genda, T.; et al. Clinical significance of cell cycle inhibitors in hepatocellular carcinoma. Med. Mol. Morphol. 2013, doi:10.1007/s00795-013-0047-7.
213. Lei, P.-P.; Zhang, Z.-J.; Shen, L.-J.; Li, J.-Y.; Zou, Q.; Zhang, H.-X. Expression and hypermethylation of p27kip1 in hepatocarcinogenesis. World J. Gastroenterol. 2005, 11, 4587-4591.
214. Calvisi, D.F.; Ladu, S.; Pinna, F.; Frau, M.; Tomasi, M.L.; Sini, M.; Simile, M.M.; Bonelli, P.; Muroni, M.R.; Seddaiu, M.A.; et al. SKP2 and CKS1 promote degradation of cell cycle regulators and are associated with hepatocellular carcinoma prognosis. Gastroenterology 2009, 137, 1816-1826.e10.
215. Fornari, F.; Gramantieri, L.; Ferracin, M.; Veronese, A.; Sabbioni, S.; Calin, G.A.; Grazi, G.L.; Giovannini, C.; Croce, C.M.; Bolondi, L. MiR-221 controls CDKN1C/p57 and CDKN1B/p27 expression in human hepatocellular carcinoma. Oncogene 2008, 27, 5651-5661.
216. Fu, X.; Wang, Q.; Chen, J.; Huang, X.; Chen, X.; Cao, L.; Tan, H.; Li, W.; Zhang, L.; Bi, J.; et al. Clinical significance of miR-221 and its inverse correlation with p27Kip1 in hepatocellular carcinoma. Mol. Biol. Rep. 2011, 38, 3029-3035.
217. Rong, M.; Chen, G.; Dang, Y. Increased miR-221 expression in hepatocellular carcinoma tissues and its role in enhancing cell growth and inhibiting apoptosis in vitro. BMC Cancer 2013, 13, 21.
218. Lee, E.-K.; Kim, D.-G.; Kim, J.-S.; Yoon, Y. Cell-cycle regulator Cks1 promotes hepatocellular carcinoma by supporting NF-κB-dependent expression of interleukin-8. Cancer Res. 2011, 71, 6827-6835.
219. Zhao, Y.; Tang, Q.; Ni, R.; Huang, X.; Wang, Y.; Lu, C.; Shen, A.; Wang, Y.; Li, C.; Yuan, Q.; et al. Early mitotic inhibitor-1, an anaphase-promoting complex/cyclosome inhibitor, can control tumor cell proliferation in hepatocellular carcinoma: Correlation with Skp2 stability and degradation of p27Kip1. Hum. Pathol. 2013, 44, 365-373.
220. Vodermaier, H.C. APC/C and SCF: Controlling each other and the cell cycle. Curr. Biol. 2004, 14, R787-R796.
221. Nakayama, K.I.; Nakayama, K. Ubiquitin ligases: Cell-cycle control and cancer. Nat. Rev. Cancer 2006, 6, 369-381.
222. Chan, C.-H.; Lee, S.-W.; Wang, J.; Lin, H.-K. Regulation of Skp2 expression and activity and its role in cancer progression. TheScientificWorldJournal 2010, 10, 1001-1015.
223. He, S.; Lu, M.; Xue, W.; Wang, Y.; Zhao, Y.; Gao, S.; Ke, Q.; Liu, Y.; Li, P.; Cui, X.; et al. Phosphorylated p27Kip1 on Thr157 is an important prognosis in human hepatocellular carcinoma in vivo and in vitro. Med. Oncol. 2010, 28, 94-104.
224. Lu, M.; Fei, M.; Cheng, C.; Wang, Y.; He, S.; Zhao, Y.; Gao, S.; Ke, Q.; Li, P.; Cui, X.; et al. Mutant p27Kip1 and its potential effect as hepatocellular gene therapy. Arch. Med. Res. 2008, 39, 573-581.
225. Matsuda, Y.; Ichida, T.; Genda, T.; Yamagiwa, S.; Aoyagi, Y.; Asakura, H. Loss of p16 contributes to p27 sequestration by cyclin D1-cyclin-dependent kinase 4 complexes and poor prognosis in hepatocellular carcinoma. Clin. Cancer Res. 2003, 9, 3389-3396.
226. Diril, M.K.; Ratnacaram, C.K.; Padmakumar, V.C.; Du, T.; Wasser, M.; Coppola, V.; Tessarollo, L.; Kaldis, P. Cyclin-dependent kinase 1 (Cdk1) is essential for cell division and suppression of DNA re-replication but not for liver regeneration. Proc. Natl. Acad. Sci. USA 2012, 109, 3826-3831.
227. Rivadeneira, D.B.; Mayhew, C.N.; Thangavel, C.; Sotillo, E.; Reed, C.A.; Graña, X.; Knudsen, E.S. Proliferative suppression by CDK4/6 inhibition: Complex function of the retinoblastoma pathway in liver tissue and hepatoma cells. Gastroenterology 2010, 138, 1920-1930.e2.
228. Roberts, P.J.; Bisi, J.E.; Strum, J.C.; Combest, A.J.; Darr, D.B.; Usary, J.E.; Zamboni, W.C.; Wong, K.-K.; Perou, C.M.; Sharpless, N.E. Multiple roles of cyclin-dependent kinase 4/6 inhibitors in cancer therapy. J. Natl. Cancer Inst. 2012, 104, 476-487.
229. Huang, X.; di Liberto, M.; Jayabalan, D.; Liang, J.; Ely, S.; Bretz, J.; Shaffer, A.L.; Louie, T.; Chen, I.; Randolph, S.; et al. Prolonged early G1 arrest by selective CDK4/CDK6 inhibition sensitizes myeloma cells to cytotoxic killing through cell cycle-coupled loss of IRF4. Blood 2012, 120, 1095-1106.