title: AEG-1/MTDH/LYRIC in liver cancer.
abstract: Hepatocellular carcinoma (HCC) is a highly virulent malignancy with diverse etiology. Identification of a common mediator of aggressive progression of HCC would be extremely beneficial not only for diagnostic/prognostic purposes but also for developing targeted therapies. AEG-1/MTDH/LYRIC gene is amplified in human HCC patients, and overexpression of AEG-1/MTDH/LYRIC has been identified in a high percentage of both hepatitis B virus and hepatitis C virus positive HCC cases, suggesting its key role in regulating hepatocarcinogenesis. Important insights into the molecular mechanisms mediating oncogenic properties of AEG-1/MTDH/LYRIC, especially regulating chemoresistance, angiogenesis, and metastasis, have been obtained from studies using HCC model. Additionally, analysis of HCC model has facilitated the identification of AEG-1/MTDH/LYRIC downstream genes and interacting proteins, thereby unraveling novel players regulating HCC development and progression leading to the development of novel interventional strategies. Characterization of a hepatocyte-specific AEG-1/MTDH/LYRIC transgenic mouse (Alb/AEG-1) has revealed novel aspects of AEG-1/MTDH/LYRIC function in in vivo contexts. Combination of AEG-1/MTDH/LYRIC inhibition and chemotherapy has documented significant efficacy in abrogating human HCC xenografts in nude mice indicating the need for developing effective AEG-1/MTDH/LYRIC inhibition strategies to obtain objective response and survival benefits in terminal HCC patients.
authors.affiliation: Department of Human and Molecular Genetics, VCU Institute of Molecular Medicine, Virginia Commonwealth University, School of Medicine, Richmond, Virginia, USA. dsarkar@vcu.edu
authors.forename: Devanand
authors.initials: D
authors.lastname: Sarkar
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000209:etiology*; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000453:epidemiology / Q000209:etiology*; D008565:Membrane Proteins; D051379:Mice; D008819:Mice, Nude; D009154:Mutation / Q000502:physiology; D011485:Protein Binding; D016601:RNA-Binding Proteins; D023041:Xenograft Model Antitumor Assays
chemical_list: D015815:Cell Adhesion Molecules; C483039:MTDH protein, human; D008565:Membrane Proteins; D016601:RNA-Binding Proteins
keywords: AEG-1; Hepatocellular carcinoma; LSF; SND1; Transgenic mouse model
references.citation: Hepatology. 2003 Feb;37(2):429-42
references.pmid: 12540794
references.citation: J Biol Chem. 2012 Jan 27;287(5):3425-32
references.pmid: 22167195
references.citation: Gene. 2005 Jun 20;353(1):8-15
references.pmid: 15927426
references.citation: Cancer Res. 1999 May 15;59(10):2370-5
references.pmid: 10344746
references.citation: Nat Rev Cancer. 2003 May;3(5):330-8
references.pmid: 12724731
references.citation: N Engl J Med. 2011 Sep 22;365(12):1118-27
references.pmid: 21992124
references.citation: J Gen Virol. 2001 Sep;82(Pt 9):2235-2241
references.pmid: 11514734
references.citation: J Gastroenterol. 2009;44 Suppl 19:102-7
references.pmid: 19148802
references.citation: Cancer Sci. 2003 Jul;94(7):633-8
references.pmid: 12841874
references.citation: Oncol Rep. 2012 Jun;27(6):2073-9
references.pmid: 22470125
references.citation: N Engl J Med. 2008 Jul 24;359(4):378-90
references.pmid: 18650514
references.citation: Gastroenterology. 2004 Feb;126(2):460-8
references.pmid: 14762783
references.citation: Clin Cancer Res. 1999 Jul;5(7):1676-81
references.pmid: 10430068
references.citation: J Natl Cancer Inst. 2005 Oct 19;97(20):1532-8
references.pmid: 16234567
references.citation: Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):12938-43
references.pmid: 19622726
references.citation: Cancer Res. 2006 Feb 1;66(3):1509-16
references.pmid: 16452207
references.citation: J Biol Chem. 2012 Feb 10;287(7):4485-91
references.pmid: 22199357
references.citation: Int J Oncol. 2004 May;24(5):1077-83
references.pmid: 15067328
references.citation: Eur J Cancer. 2007 Apr;43(6):979-92
references.pmid: 17291746
references.citation: EMBO J. 2002 Sep 16;21(18):4950-8
references.pmid: 12234934
references.citation: Cancer Cell. 2004 Apr;5(4):365-74
references.pmid: 15093543
references.citation: J Virol. 2001 Feb;75(3):1401-7
references.pmid: 11152513
references.citation: Gene. 2004 Dec 8;343(1):23-40
references.pmid: 15563829
references.citation: Nature. 2003 Sep 25;425(6956):411-4
references.pmid: 14508492
references.citation: Hepatology. 2007 Jan;45(1):42-52
references.pmid: 17187432
references.citation: Endocr Rev. 1999 Dec;20(6):761-87
references.pmid: 10605625
references.citation: Am J Epidemiol. 2002 Feb 15;155(4):323-31
references.pmid: 11836196
references.citation: Drug Discov Today. 2009 Mar;14(5-6):278-83
references.pmid: 19073276
references.citation: Nucleic Acids Res. 2008 Aug;36(13):4474-87
references.pmid: 18603592
references.citation: Mol Endocrinol. 2003 Sep;17(9):1805-14
references.pmid: 12819296
references.citation: Nat Rev Cancer. 2008 Mar;8(3):212-26
references.pmid: 18292776
references.citation: Cancer Res. 2008 Mar 1;68(5):1478-84
references.pmid: 18316612
references.citation: Nat Rev Cancer. 2006 Sep;6(9):674-87
references.pmid: 16929323
references.citation: Cancer Res. 2010 Apr 15;70(8):3249-58
references.pmid: 20388796
references.citation: CA Cancer J Clin. 2012 Jan-Feb;62(1):10-29
references.pmid: 22237781
references.citation: Oncogene. 2008 Feb 14;27(8):1114-21
references.pmid: 17704808
references.citation: Semin Liver Dis. 1999;19(3):329-38
references.pmid: 10518312
references.citation: Hepatology. 2008 Oct;48(4):1312-27
references.pmid: 18821591
references.citation: Int J Cancer. 2012 Jan 15;130(2):319-27
references.pmid: 21328580
references.citation: Hepatology. 2007 May;45(5):1298-305
references.pmid: 17464972
references.citation: Nature. 1991 Apr 4;350(6317):429-31
references.pmid: 1672732
references.citation: Cancer Biol Ther. 2007 Mar;6(3):354-9
references.pmid: 17312390
references.citation: Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17390-5
references.pmid: 17088530
references.citation: Gut. 2005 Aug;54(8):1162-8
references.pmid: 16009689
references.citation: Hepatology. 2012 Nov;56(5):1782-91
references.pmid: 22689379
references.citation: Clin Cancer Res. 2011 Nov 1;17(21):6693-701
references.pmid: 21908579
references.citation: ACS Chem Biol. 2007 May 22;2(5):329-36
references.pmid: 17465519
references.citation: J Clin Oncol. 2006 Apr 20;24(12):1898-903
references.pmid: 16622265
references.citation: EMBO J. 2000 Sep 1;19(17):4665-75
references.pmid: 10970859
references.citation: Lung Cancer. 2005 Sep;49(3):345-51
references.pmid: 15993511
references.citation: Am J Cancer Res. 2012;2(3):269-85
references.pmid: 22679558
references.citation: Ann Surg Oncol. 2008 Apr;15(4):962-71
references.pmid: 18236113
references.citation: Oncologist. 2007 Dec;12(12):1425-32
references.pmid: 18165619
references.citation: J Clin Invest. 2009 Mar;119(3):465-77
references.pmid: 19221438
references.citation: Semin Cancer Biol. 2011 Feb;21(1):10-20
references.pmid: 20969960
references.citation: Ann Surg. 2001 Jul;234(1):63-70
references.pmid: 11420484
references.citation: Proc Natl Acad Sci U S A. 2009 Dec 15;106(50):21300-5
references.pmid: 19940250
references.citation: Lancet. 2002 May 18;359(9319):1734-9
references.pmid: 12049862
references.citation: Oncogene. 2009 Oct 15;28(41):3663-70
references.pmid: 19648967
references.citation: Am J Pathol. 1997 Apr;150(4):1141-57
references.pmid: 9094970
references.citation: Cell. 2008 Feb 8;132(3):363-74
references.pmid: 18267069
references.citation: J Biol Chem. 2012 Apr 20;287(17):13952-8
references.pmid: 22396537
references.citation: Gastroenterology. 2007 Jun;132(7):2557-76
references.pmid: 17570226
references.citation: Cell Cycle. 2009 Jul 15;8(14):2146-51
references.pmid: 19556876
references.citation: Nat Rev Gastroenterol Hepatol. 2010 Aug;7(8):448-58
references.pmid: 20628345
references.citation: J Hepatol. 2011 Dec;55(6):1317-24
references.pmid: 21703197
references.citation: World J Gastroenterol. 2007 Apr 28;13(16):2271-82
references.pmid: 17511024
references.citation: Cancer J. 2008 Mar-Apr;14(2):117-22
references.pmid: 18391617
references.citation: Hepatology. 2010 May;51(5):1820-32
references.pmid: 20432259
references.citation: N Engl J Med. 2003 Apr 24;348(17):1625-38
references.pmid: 12711737
references.citation: Hepatology. 2011 May;53(5):1538-48
references.pmid: 21520169
references.citation: Clin Cancer Res. 2011 Dec 1;17(23):7294-302
references.pmid: 21976539
references.citation: Nat Rev Immunol. 2005 Mar;5(3):215-29
references.pmid: 15738952
references.citation: Mol Ther. 2013 Apr;21(4):758-66
references.pmid: 23319057
references.citation: Nature. 1980 Jul 31;286(5772):533-5
references.pmid: 6250074
references.citation: Nature. 2004 Sep 23;431(7007):461-6
references.pmid: 15329734
references.citation: Proc Natl Acad Sci U S A. 2010 May 4;107(18):8357-62
references.pmid: 20404171
references.citation: Cell. 2006 Jun 30;125(7):1253-67
references.pmid: 16814713
references.citation: Proc Natl Acad Sci U S A. 2012 Mar 20;109(12):4503-8
references.pmid: 22396589
references.citation: J Hepatol. 2010 Feb;52(2):252-7
references.pmid: 20022654
references.citation: Nucleic Acids Res. 2007;35(13):4485-94
references.pmid: 17576664
references.citation: Lancet. 2003 Dec 6;362(9399):1907-17
references.pmid: 14667750
references.citation: Oncogene. 1998 May 14;16(19):2459-67
references.pmid: 9627112
references.citation: Oncogene. 2002 May 16;21(22):3592-602
references.pmid: 12032861