Epigenetic regulation of WNT signaling in chronic lymphocytic leukemia.
Certain WNT and WNT network target genes are expressed at higher or lower levels in chronic lymphocytic leukemia compared with normal B-cells. This includes upregulation of nuclear complex genes, as well as genes for cytoplasmic proteins and WNT ligands and their cognate receptors. In addition, epigenetic silencing of several negative regulators of the WNT pathway have been identified. The balance between epigenetic downregulation of negative effector genes and increased expression of positive effector genes demonstrate that the epigenetic downregulation of WNT antagonists is one mechanism, perhaps the main mechanism, that is permissive to active WNT signaling in chronic lymphocytic leukemia. Moreover, constitutive activation of the WNT network and target genes is likely to impact on additional interacting signaling pathways. Based on published studies, we propose a model of WNT signaling that involves mainly permissive expression, and sometimes overexpression, of positive effectors and downregulation of negative regulators in the network. In this model, DNA methylation, histone modifications and altered expression of microRNA molecules interact to allow continuous WNT signaling.
Bennett
Lynda B
LB
Taylor
Kristen H
KH
Arthur
Gerald L
GL
Rahmatpanah
Farahnaz B
FB
Hooshmand
Sam I
SI
Caldwell
Charles W
CW
Leukemia. 2009 Jun;23(6):1159-63
19158830
Nature. 2000 Jul 6;406(6791):86-90
10894547
Trends Biochem Sci. 2008 Dec;33(12):592-600
18926707
Haematologica. 2010 Jan;95(1):110-8
19713228
Mol Cell Biol. 2007 Dec;27(23):8164-77
17923689
Blood. 2006 Nov 1;108(9):3143-51
16840734
Bioessays. 2008 Nov;30(11-12):1110-25
18937364
Carcinogenesis. 2007 Jan;28(1):60-70
16774933
Cell Signal. 2009 Nov;21(11):1541-7
19298854
Cancer Res. 2005 Dec 15;65(24):11241-6
16357125
Mol Cell. 2008 May 23;30(4):507-18
18498752
Leukemia. 2009 Jun;23(6):1019-28
19194470
Leukemia. 2006 Oct;20(10):1855-62
16900213
Blood. 2009 Apr 16;113(16):3744-53
19096009
Curr Drug Targets. 2009 Jul;10(7):620-31
19601766
Proc Natl Acad Sci U S A. 2008 Oct 7;105(40):15417-22
18824696
Leuk Lymphoma. 2005 Sep;46(9):1275-85
16109604
Philos Trans R Soc Lond B Biol Sci. 2008 Apr 12;363(1495):1333-47
18192173
Leukemia. 2007 May;21(5):965-72
17344921
Hepatology. 2009 Aug;50(2):472-80
19585654
Nat Rev Mol Cell Biol. 2009 Apr;10(4):276-86
19305417
Nat Struct Mol Biol. 2009 Mar;16(3):304-311
19234465
RNA. 2009 Aug;15(8):1443-61
19561119
Science. 2001 Aug 10;293(5532):1074-80
11498575
PLoS One. 2009 Jul 31;4(7):e6459
19649288
Bioinformatics. 2006 Jul 15;22(14):e431-9
16873504
Blood. 2009 Jan 22;113(4):856-65
18796623
Blood. 2009 Oct 29;114(18):3872-9
19717645
Methods Mol Biol. 2009;563:303-52
19597793
BMC Cancer. 2009 May 21;9:159
19460168
Nucleic Acids Res. 2009 Jan;37(Database issue):D155-8
18957447
Clin Cancer Res. 2008 Jan 15;14(2):396-404
18223214
Proc Natl Acad Sci U S A. 2007 Nov 13;104(46):18151-6
17989227
Cancer Lett. 2009 Nov 28;285(2):116-26
19464788
Nature. 2009 Jul 2;460(7251):66-72
19571879
Science. 2007 Oct 19;318(5849):447-50
17761849
Hematol Oncol. 2006 Sep;24(3):134-8
16841369
Cell Signal. 2008 May;20(5):795-802
18160255
Cancer Cell. 2003 Nov;4(5):349-60
14667502
J Biol Chem. 2008 Jun 13;283(24):16818-29
18408217
Blood. 2009 May 28;113(22):5568-74
19336759
Leuk Lymphoma. 2009 Mar;50(3):419-26
19347729
BMC Immunol. 2006 Jun 29;7:13
16808837
Br J Cancer. 2009 Aug 18;101(4):699-706
19638978
Cancer Res. 2008 Nov 1;68(21):8743-51
18974116
Blood. 2007 Jul 15;110(2):735-42
17463171
Genes Dev. 2006 May 1;20(9):1123-36
16618801
Nature. 2007 Aug 2;448(7153):553-60
17603471
Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):3118-23
14973184
Cell Signal. 2007 Apr;19(4):659-71
17188462
Leuk Res. 2006 Jan;30(1):29-32
16054689
Nat Genet. 2006 Dec;38(12):1359-60
17133218
Epigenetics. 2009 Jul 1;4(5):307-312
28001119
Endocr Rev. 2005 Dec;26(7):898-915
16126938
Pharmacol Ther. 2009 Sep;123(3):344-52
19464317
Braz J Med Biol Res. 2007 Nov;40(11):1435-40
17934639
J Clin Oncol. 2009 Nov 10;27(32):5459-68
19826124
Ann N Y Acad Sci. 2007 Apr;1100:60-74
17460165
BMC Bioinformatics. 2005 Jan 20;6:12
15661078
Cancer Res. 2006 Jan 15;66(2):653-8
16423993
Eur J Cancer. 2009 May;45(7):1129-1136
19211243
Nat Med. 2007 Aug;13(8):944-51
17632527
Cell Signal. 2008 Jun;20(6):1198-208
18396013
J Cell Biol. 2009 Jun 1;185(5):811-26
19487454
Genes Chromosomes Cancer. 2009 Sep;48(9):828-41
19530241
Blood. 2009 Nov 5;114(19):4179-85
19745069
Leukemia. 2007 May;21(5):949-55
17361218
Leuk Res. 2010 Feb;34(2):221-8
19682743
J Mol Biol. 2009 Aug 28;391(4):691-702
19576224
J Immunol. 2002 Jul 15;169(2):758-69
12097378
J Clin Invest. 2005 Mar;115(3):755-64
15711642
Exp Hematol. 2002 Jan;30(1):26-33
11823034
Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):3047-52
18287027
Mol Cell Biol. 2007 Nov;27(22):7802-15
17875931
Int J Mol Med. 2009 Jun;23(6):763-9
19424602
N Engl J Med. 2005 Oct 27;353(17):1793-801
16251535
Cell Signal. 2008 Oct;20(10):1697-704
18555664
Int J Biochem Cell Biol. 2010 Mar;42(3):381-90
19631281
Cell Cycle. 2007 May 2;6(9):1001-5
17457051
Stem Cells. 2004;22(5):849-60
15342948
Dev Dyn. 2010 Jan;239(1):56-68
19655378
Gene. 2002 Apr 17;288(1-2):119-27
12034501
J Biol Chem. 2009 Jan 30;284(5):3323-3333
19047045
Nature. 2006 Feb 16;439(7078):871-4
16357870
Hum Mol Genet. 2005 Apr 15;14 Spec No 1:R93-R100
15809278
Nat Genet. 2007 Feb;39(2):232-6
17200670
Proc Natl Acad Sci U S A. 2007 Oct 2;104(40):15805-10
17890317
Cancer Res. 2009 Mar 15;69(6):2623-9
19258506
Leukemia. 2009 Nov;23(11):2118-28
19657365
Carcinogenesis. 2006 Jun;27(6):1121-5
16699174
Stem Cells. 2005 Sep;23(8):1180-91
15955826
Curr Oncol Rep. 2007 Sep;9(5):345-52
17706162
Exp Cell Res. 2009 Oct 15;315(17):2941-52
19591824
Exp Cell Res. 2009 Oct 1;315(16):2690-704
19563800
Eur J Cancer. 2009 May;45(7):1137-1145
19346125
Histol Histopathol. 2009 Mar;24(3):385-98
19130408
J Biol Chem. 2005 Mar 11;280(10):9498-508
15618220
Cell. 2007 May 18;129(4):823-37
17512414
Br J Haematol. 2009 Nov;147(4):471-83
19751240
Blood. 2009 Jul 9;114(2):404-14
19398721
J Clin Oncol. 2008 Sep 20;26(27):4497-503
18662968
Best Pract Res Clin Haematol. 2007 Sep;20(3):385-97
17707828
PLoS One. 2009 Sep 11;4(9):e6986
19750229
Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15524-9
12434020
Blood. 1995 May 15;85(10):2870-6
7742549
Blood. 1992 Oct 15;80(8):2074-80
1382719
Leuk Res. 2006 Sep;30(9):1135-9
16427695
Cell Death Differ. 2010 Feb;17(2):215-20
19498445
Curr Med Chem. 2009;16(17):2075-85
19519382
Cancer Res. 2009 Apr 15;69(8):3278-82
19351815
Blood. 2009 Jun 18;113(25):6411-8
19211935
Cell. 2007 Feb 23;128(4):669-81
17320505
Blood. 2009 Oct 15;114(16):3367-75
19636060
J Biol Chem. 2003 Nov 14;278(46):45937-45
12928438
Bioinformatics. 2009 Aug 1;25(15):1991-3
19435746
RNA. 2007 Feb;13(2):223-39
17185360
Nat Chem Biol. 2009 Feb;5(2):100-7
19125156
Nat Med. 2008 Nov;14(11):1271-7
18931683
Annu Rev Med. 2009;60:167-79
19630570
Blood. 2005 Feb 1;105(3):959-67
15466934
Lab Invest. 2009 Jun;89(6):708-16
19349957
J Exp Med. 2001 Dec 3;194(11):1639-47
11733578
Blood. 2007 Jun 1;109(11):4944-51
17327404
J Immunol. 2005 Mar 15;174(6):3749-56
15749915
J Cell Biochem. 2009 Feb 1;106(2):337-43
19115259
Cancer Biol Ther. 2004 Oct;3(10):989-94
15467427
J Pathol. 2008 May;215(1):13-20
18348159
Cancer Biol Ther. 2006 Sep;5(9):1059-64
16940750
Clin Cancer Res. 2009 Jun 15;15(12):3970-7
19509171
Epigenomics. 2009 Oct;1(1):39-61
20495622
Nat Rev Drug Discov. 2006 Dec;5(12):997-1014
17139285
Cancer Res. 2004 Apr 1;64(7):2424-33
15059895
Int J Oncol. 2009 May;34(5):1411-5
19360354
Mol Cancer Res. 2008 Dec;6(12):1928-36
19074837
J Biol Chem. 2002 Nov 1;277(44):41762-9
12205098
J Clin Pathol. 2008 Nov;61(11):1214-9
18765431
Nat Rev Genet. 2007 Apr;8(4):286-98
17339880
J Clin Oncol. 2009 Aug 10;27(23):3808-14
19470922
Cell. 2005 Jan 28;120(2):169-81
15680324
Leukemia. 2008 Feb;22(2):330-8
17989717
Clin Cancer Res. 2007 Jul 15;13(14):4042-5
17634527
Mol Cell Biol. 2007 Nov;27(21):7560-73
17785445
J Cell Biol. 2008 Mar 24;180(6):1087-100
18347071
J Cell Biol. 2003 Sep 1;162(5):899-908
12952940
Genes Dev. 2004 Jul 1;18(13):1592-605
15231737
Cancer Res. 2008 Jun 1;68(11):4116-22
18519670
Bioorg Med Chem. 2009 Sep 1;17(17):6257-63
19665384
Int J Cancer. 2010 Mar 1;126(5):1109-20
19653274
Blood. 2009 Nov 26;114(23):4832-42
19789386
Int J Biochem Cell Biol. 2009 Jan;41(1):87-95
18834952
J Cell Biochem. 2007 Aug 1;101(5):1109-24
17546602
Cell Res. 2009 Jan;19(1):71-88
19002158