title: Drug resistance mediated by AEG-1/MTDH/LYRIC.
abstract: AEG-1/MTDH/LYRIC has been shown to promote cancer progression and development. Overexpression of AEG-1/MTDH/LYRIC correlates with angiogenesis, metastasis, and chemoresistance to various chemotherapy agents in cancer cells originating from a variety of tissues. In this chapter, we focus on the role of AEG-1/MTDH/LYRIC in drug resistance. Mechanistic studies have shown that AEG-1/MTDH/LYRIC is involved in classical oncogenic pathways including Ha-Ras, myc, NFκB, and PI3K/Akt. AEG-1/MTDH/LYRIC also promotes protective autophagy by activating AMP kinase and autophagy-related gene 5. Another reported mechanism by which AEG-1/MTDH/LYRIC regulates drug resistance is by increasing loading of multidrug resistance gene (MDR) 1 mRNA to the polysome, thereby facilitating MDR1 protein translation. More recently, a novel function for AEG-1/MTDH/LYRIC as an RNA-binding protein was elucidated, which has the potential to impact expression of drug sensitivity or resistance genes. Finally, AEG-1/MTDH/LYRIC acts in microRNA-directed gene silencing via an interaction with staphylococcal nuclease and tudor domain containing 1, a component of the RNA-induced silencing complex. Altered microRNA expression and activity induced by AEG-1/MTDH/LYRIC represent an additional way that AEG-1/MTDH/LYRIC may cause drug resistance in cancer. The multiple functions of AEG-1/MTDH/LYRIC in drug resistance highlight that it is a viable target as an anticancer agent for a wide variety of cancers.
authors.affiliation: Department of Obstetrics and Gynecology, The University of Iowa, Iowa City, Iowa, USA. xiangbing-meng@uiowa.edu
authors.forename: Xiangbing
authors.initials: X
authors.lastname: Meng
authors.forename: Kristina W
authors.initials: KW
authors.lastname: Thiel
authors.forename: Kimberly K
authors.initials: KK
authors.lastname: Leslie
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000235:genetics; D001343:Autophagy / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000502:physiology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D006801:Humans; D008565:Membrane Proteins; D046228:Microarray Analysis; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics*; D016601:RNA-Binding Proteins
chemical_list: D000970:Antineoplastic Agents; D015815:Cell Adhesion Molecules; C483039:MTDH protein, human; D008565:Membrane Proteins; D016601:RNA-Binding Proteins
keywords: AEG-1/MTDH/LYRIC; Chemoresistance; NFκB; SND1; miR-375
references.citation: Oncogene. 2007 Dec 6;26(55):7647-55
references.pmid: 17563745
references.citation: Oncogene. 2008 Feb 14;27(8):1114-21
references.pmid: 17704808
references.citation: J Biol Chem. 2005 Apr 15;280(15):14989-96
references.pmid: 15695802
references.citation: Crit Rev Biochem Mol Biol. 2013 Jan-Feb;48(1):51-68
references.pmid: 23163351
references.citation: Proc Natl Acad Sci U S A. 2009 Dec 15;106(50):21300-5
references.pmid: 19940250
references.citation: Clin Cancer Res. 2009 Sep 15;15(18):5615-20
references.pmid: 19723648
references.citation: J Hepatol. 2011 Dec;55(6):1317-24
references.pmid: 21703197
references.citation: Cancer Immunol Immunother. 2011 Jun;60(6):883-93
references.pmid: 21400023
references.citation: Breast Cancer. 2014 May;21(3):341-9
references.pmid: 22903204
references.citation: Nat Med. 2010 Feb;16(2):214-8
references.pmid: 20098429
references.citation: Proc Natl Acad Sci U S A. 2010 Dec 21;107(51):22243-8
references.pmid: 21127263
references.citation: Oncogene. 2011 Oct 27;30(43):4386-98
references.pmid: 21552288
references.citation: Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):12938-43
references.pmid: 19622726
references.citation: Neuroscience. 2011 Dec 29;199:359-67
references.pmid: 22020319
references.citation: Pharmacol Ther. 2011 Apr;130(1):1-8
references.pmid: 21256156
references.citation: Clin Cancer Res. 2012 Oct 15;18(20):5617-27
references.pmid: 22904106
references.citation: J Biol Chem. 2012 Feb 10;287(7):4485-91
references.pmid: 22199357
references.citation: Nucleic Acids Res. 2011 May;39(9):3892-902
references.pmid: 21245048
references.citation: Cancer Res. 2006 Feb 1;66(3):1509-16
references.pmid: 16452207
references.citation: Cancer Biol Ther. 2012 Jan 1;13(1):43-9
references.pmid: 22336587
references.citation: Cancer Res. 2011 Dec 15;71(24):7481-9
references.pmid: 22037872
references.citation: Cancer Cell. 2004 Apr;5(4):365-74
references.pmid: 15093543
references.citation: FASEB J. 2010 Sep;24(9):3370-80
references.pmid: 20453113
references.citation: J Hum Genet. 2011 Aug;56(8):595-601
references.pmid: 21753766
references.citation: Genes Chromosomes Cancer. 2006 Nov;45(11):1033-40
references.pmid: 16897746
references.citation: Breast Cancer Res Treat. 2013 Feb;137(3):689-96
references.pmid: 23271328
references.citation: Oncogene. 2009 Jul 2;28(26):2476-84
references.pmid: 19448665
references.citation: Proc Natl Acad Sci U S A. 2011 Oct 25;108(43):E943-51
references.pmid: 21949371
references.citation: Oncogene. 2010 Oct 28;29(43):5785-95
references.pmid: 20711237
references.citation: FEBS J. 2011 Sep;278(18):3226-45
references.pmid: 21740521
references.citation: Oncogene. 2012 Jan 5;31(1):39-47
references.pmid: 21666713
references.citation: Mol Med Rep. 2012 May;5(5):1299-304
references.pmid: 22377847
references.citation: Cancer Res. 2008 Mar 1;68(5):1478-84
references.pmid: 18316612
references.citation: Cancer Res. 2010 Apr 15;70(8):3249-58
references.pmid: 20388796
references.citation: Cancer Cell. 2009 Jan 6;15(1):9-20
references.pmid: 19111877
references.citation: PLoS One. 2012;7(12):e51561
references.pmid: 23240043
references.citation: Glycobiology. 2006 Nov;16(11):137R-157R
references.pmid: 16840800
references.citation: PLoS One. 2011;6(6):e20920
references.pmid: 21687633
references.citation: Clin Transl Oncol. 2008 Aug;10(8):462-7
references.pmid: 18667376
references.citation: Int J Gynecol Pathol. 2011 Mar;30(2):145-50
references.pmid: 21293286
references.citation: Gynecol Oncol. 2011 Aug;122(2):366-71
references.pmid: 21571355
references.citation: Mol Cell. 1998 Oct;2(4):417-25
references.pmid: 9809063
references.citation: Nat Med. 1999 Feb;5(2):157-63
references.pmid: 9930862
references.citation: Hepatology. 2012 Nov;56(5):1782-91
references.pmid: 22689379
references.citation: J Biol Chem. 2011 Jun 3;286(22):19982-92
references.pmid: 21478147
references.citation: J Clin Invest. 2009 Mar;119(3):465-77
references.pmid: 19221438
references.citation: Oncol Rep. 2012 May;27(5):1520-6
references.pmid: 22367022
references.citation: Gastroenterology. 2006 Oct;131(4):1262-70
references.pmid: 17030195
references.citation: Genes Chromosomes Cancer. 2013 Jan;52(1):56-68
references.pmid: 22987659
references.citation: Oncol Lett. 2011 May;2(3):399-405
references.pmid: 22866094
references.citation: Gene. 2005 Jun 20;353(1):8-15
references.pmid: 15927426
references.citation: Cancer Res. 2010 Jan 1;70(1):172-80
references.pmid: 19996285
references.citation: J Hum Genet. 2012 Sep;57(9):556-63
references.pmid: 22718022
references.citation: Curr Drug Targets. 2011 Aug;12(9):1256-66
references.pmid: 21443467
references.citation: Cell Biosci. 2011 Nov 07;1(1):36
references.pmid: 22060137
references.citation: Clin Cancer Res. 2012 Oct 15;18(20):5554-61
references.pmid: 23071357
references.citation: Electrophoresis. 2000 Aug;21(14):3048-57
references.pmid: 11001322
references.citation: Cancer Res. 2012 May 1;72(9):2440-53
references.pmid: 22379025
references.citation: Oncogene. 2013 Feb 28;32(9):1173-82
references.pmid: 22508479
references.citation: Cancer Res. 2010 Nov 15;70(22):8977-80
references.pmid: 20978194
references.citation: J Surg Oncol. 2011 Feb;103(2):184-92
references.pmid: 21259255
references.citation: Neurosci Lett. 2012 Dec 7;531(2):204-8
references.pmid: 23103713
references.citation: Cell. 2006 Nov 3;127(3):635-48
references.pmid: 17081983
references.citation: Oncogene. 2012 Jul 12;31(28):3357-69
references.pmid: 22056881
references.citation: Oncogene. 2009 Oct 15;28(41):3663-70
references.pmid: 19648967
references.citation: Histopathology. 2012 May;60(6):953-63
references.pmid: 22372608
references.citation: Eur J Pharmacol. 2009 Dec 25;625(1-3):63-72
references.pmid: 19836385
references.citation: J Biol Chem. 2012 Apr 20;287(17):13952-8
references.pmid: 22396537
references.citation: Int J Oncol. 2012 Sep;41(3):985-94
references.pmid: 22752059
references.citation: Clin Cancer Res. 2009 May 1;15(9):3003-13
references.pmid: 19383828
references.citation: Nat Genet. 2008 Jan;40(1):43-50
references.pmid: 18066065
references.citation: Cell. 2005 Jan 28;120(2):237-48
references.pmid: 15680329
references.citation: Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7
references.pmid: 18669648
references.citation: Front Biosci (Elite Ed). 2012 Jan 01;4:410-25
references.pmid: 22201883
references.citation: Leuk Res Treatment. 2012;2012:671702
references.pmid: 23259070
references.citation: Hepatology. 2011 May;53(5):1538-48
references.pmid: 21520169
references.citation: J Hepatol. 2012 Feb;56(2):389-96
references.pmid: 21888875
references.citation: J Biol Chem. 2013 Mar 1;288(9):6034-44
references.pmid: 23300087
references.citation: J Int Med Res. 2012;40(5):1662-9
references.pmid: 23206448
references.citation: Proc Natl Acad Sci U S A. 2012 Mar 20;109(12):4503-8
references.pmid: 22396589
references.citation: RNA. 2012 Mar;18(3):462-71
references.pmid: 22240577