دورية أكاديمية

Inhibition of C-terminal binding protein attenuates transcription factor 4 signaling to selectively target colon cancer stem cells.

التفاصيل البيبلوغرافية
العنوان: Inhibition of C-terminal binding protein attenuates transcription factor 4 signaling to selectively target colon cancer stem cells.
المؤلفون: Patel J; a Hunter Holmes McGuire VA Medical Center ; Richmond , VA USA., Baranwal S, Love IM, Patel NJ, Grossman SR, Patel BB
المصدر: Cell cycle (Georgetown, Tex.) [Cell Cycle] 2014; Vol. 13 (22), pp. 3506-18.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: Taylor & Francis Country of Publication: United States NLM ID: 101137841 Publication Model: Print Cited Medium: Internet ISSN: 1551-4005 (Electronic) Linking ISSN: 15514005 NLM ISO Abbreviation: Cell Cycle Subsets: MEDLINE
أسماء مطبوعة: Publication: 2015- : Philadelphia, PA : Taylor & Francis
Original Publication: Georgetown, TX : Landes Bioscience, c2002-
مواضيع طبية MeSH: Alcohol Oxidoreductases/*metabolism , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/*metabolism , Colonic Neoplasms/*genetics , DNA-Binding Proteins/*metabolism , Neoplastic Stem Cells/*pathology , Transcription Factors/*metabolism, Alcohol Oxidoreductases/genetics ; Apoptosis/genetics ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics ; Colonic Neoplasms/pathology ; DNA-Binding Proteins/genetics ; Gene Expression Regulation, Neoplastic ; Humans ; Protein Binding/genetics ; Signal Transduction/genetics ; Transcription Factor 4 ; Transcription Factors/genetics ; beta Catenin/genetics
مستخلص: Selective targeting of cancer stem cells (CSCs), implicated in tumor relapse, holds great promise in the treatment of colorectal cancer. Overexpression of C-terminal binding protein (CtBP), an NADH dependent transcriptional regulator, is often observed in colon cancer. Of note, TCF-4 signaling is also up-regulated in colonic CSCs. We hypothesized that CtBP, whose dehydrogenase activity is amenable to pharmacological inhibition by 4-methylthio-2-oxobutyric acid (MTOB), positively regulates TCF-4 signaling, leading to CSC growth and self-renewal. CSCs demonstrated significant upregulation of CtBP1 and CtBP2 levels (mRNA and protein) and activity partly due to increased NADH/NAD ratio, as well as increased TCF/LEF transcriptional activity, compared to respective controls. Depletion of CtBP2 inhibited, while its overexpression enhanced, CSC growth (1° spheroids) and self-renewal (2°/3° spheroids). Similarly, MTOB caused a robust inhibition of spheroid growth and self-renewal in a dose dependent manner. MTOB displayed significantly greater selectivity for growth inhibition in the spheroids, at least in part through induction of apoptosis, compared to monolayer controls. Moreover, MTOB inhibited basal as well as induced (by GSK-3β inhibitor) TCF/LEF activity while suppressing mRNA and protein levels of several β-catenin target genes (CD44, Snail, C-MYC and LGR5). Lastly, CtBP physically interacted with TCF-4, and this interaction was significantly inhibited in the presence of MTOB. The above findings point to a novel role of CtBPs in the promotion of CSC growth and self-renewal through direct regulation of TCF/LEF transcription. Moreover, small molecular inhibition of its function can selectively target CSCs, presenting a novel approach for treatment of colorectal cancer focused on targeting of CSCs.
References: Oncogene. 2010 Dec 16;29(50):6603-8. (PMID: 20818429)
Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4568-73. (PMID: 12676992)
BioDrugs. 2007;21(5):299-310. (PMID: 17896836)
Cancer Res. 2003 Apr 15;63(8):1906-13. (PMID: 12702582)
Science. 1998 Sep 4;281(5382):1509-12. (PMID: 9727977)
Cancer Res. 2006 Oct 1;66(19):9339-44. (PMID: 16990346)
Nature. 2007 Oct 25;449(7165):1003-7. (PMID: 17934449)
Proc Natl Acad Sci U S A. 2011 Mar 15;108(11):4382-7. (PMID: 21368208)
Pharm Res. 2011 Apr;28(4):827-38. (PMID: 21161336)
PLoS One. 2012;7(9):e46391. (PMID: 23050024)
Cell Cycle. 2010 Sep 15;9(18):3645-6. (PMID: 20930508)
Cell Stem Cell. 2008 Nov 6;3(5):508-18. (PMID: 18983966)
Colorectal Dis. 2012 Feb;14(2):e31-47. (PMID: 21848897)
Genes Dev. 2003 May 15;17(10):1253-70. (PMID: 12756227)
Oncotarget. 2013 Feb;4(2):184-91. (PMID: 23468473)
Genes Cancer. 2012 Jul;3(7-8):481-90. (PMID: 23264848)
Cancer Treat Rev. 2013 May;39(3):290-6. (PMID: 23219150)
Mol Cancer. 2010;9:212. (PMID: 20691072)
Science. 2007 Nov 16;318(5853):1108-13. (PMID: 17932254)
FEBS Lett. 2003 Feb 27;537(1-3):157-60. (PMID: 12606049)
Int J Cell Biol. 2013;2013:647975. (PMID: 23762064)
Nat Protoc. 2009;4(4):495-505. (PMID: 19300443)
Cell Cycle. 2010 Sep 15;9(18):3740-50. (PMID: 20930544)
Biochim Biophys Acta. 1995 Nov 9;1269(2):153-61. (PMID: 7488648)
Biochem Pharmacol. 2006 Sep 28;72(7):806-15. (PMID: 16870157)
Oncogene. 2006 Jul 27;25(32):4441-8. (PMID: 16547505)
Nucleic Acids Res. 2003 May 1;31(9):2369-80. (PMID: 12711682)
Oncotarget. 2010 Nov;1(7):552-66. (PMID: 21317452)
PLoS One. 2010;5(4):e10024. (PMID: 20383323)
Cancer Res. 2009 Oct 1;69(19):7507-11. (PMID: 19752085)
Transl Oncol. 2013 Dec 01;6(6):649-59. (PMID: 24466367)
Mol Cell. 2002 Feb;9(2):213-24. (PMID: 11864595)
Science. 2013 Mar 29;339(6127):1567-70. (PMID: 23539597)
Stem Cells. 2012 Mar;30(3):363-71. (PMID: 22232074)
Science. 2002 Mar 8;295(5561):1895-7. (PMID: 11847309)
Cell. 2002 Oct 18;111(2):241-50. (PMID: 12408868)
Nature. 2001 Nov 1;414(6859):105-11. (PMID: 11689955)
J Biol Chem. 2001 Nov 30;276(48):45113-9. (PMID: 11572874)
EMBO J. 2006 Jun 21;25(12):2735-45. (PMID: 16710294)
Immunity. 2013 Sep 19;39(3):611-21. (PMID: 24012420)
Nature. 2005 Apr 14;434(7035):843-50. (PMID: 15829953)
Nat Commun. 2013;4:1449. (PMID: 23385593)
Development. 1999 Jun;126(14):3159-70. (PMID: 10375506)
Curr Med Chem. 2009;16(14):1688-703. (PMID: 19442140)
Nature. 2009 Apr 9;458(7239):780-3. (PMID: 19194462)
Cell. 2009 Aug 21;138(4):645-59. (PMID: 19682730)
Mol Cell Biol. 1999 Jan;19(1):777-87. (PMID: 9858600)
Nature. 2012 Jul 19;487(7407):330-7. (PMID: 22810696)
معلومات مُعتمدة: I01 BX000837 United States BX BLRD VA
فهرسة مساهمة: Keywords: 1°, primary; 2°, secondary; 3°, tertiary; C-terminal binding protein; CSC, cancer stem cell; CtBP, c-terminal binding protein; TCF-4; TCF-4, transcription factor 4; apoptosis; cancer stem cells; β-catenin
المشرفين على المادة: 0 (Basic Helix-Loop-Helix Leucine Zipper Transcription Factors)
0 (DNA-Binding Proteins)
0 (TCF4 protein, human)
0 (Transcription Factor 4)
0 (Transcription Factors)
0 (beta Catenin)
EC 1.1.- (Alcohol Oxidoreductases)
EC 1.1.1.- (C-terminal binding protein)
تواريخ الأحداث: Date Created: 20141209 Date Completed: 20150916 Latest Revision: 20220321
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC4613182
DOI: 10.4161/15384101.2014.958407
PMID: 25483087
قاعدة البيانات: MEDLINE