CtBP- an emerging oncogene and novel small molecule drug target: Advances in the understanding of its oncogenic action and identification of therapeutic inhibitors

Cancer Biology & Therapy
M Michael DconaS R Grossman

Abstract

C-terminal Binding Proteins (CtBP) 1 and 2 are oncogenic transcriptional co-regulators overexpressed in many cancer types, with their expression level correlating to worse prognostic outcomes and aggressive tumor features. CtBP negatively regulates the expression of many tumor suppressor genes, while coactivating genes that promote proliferation, epithelial-mesenchymal transition, and cancer stem cell self-renewal activity. In light of this evidence, the development of novel inhibitors that mitigate CtBP function may provide clinically actionable therapeutic tools. This review article focuses on the progress made in understanding CtBP structure, role in tumor progression, and discovery and development of CtBP inhibitors that target CtBP's dehydrogenase activity and other functions, with a focus on the theory and rationale behind the designs of current inhibitors. We provide insight into the future development and use of rational combination therapy that may further augment the efficacy of CtBP inhibitors, specifically addressing metastasis and cancer stem cell populations within tumors.

References

Aug 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·C Bello-FernandezJ L Cleveland
May 1, 2001·The Journal of Biological Chemistry·S PalmerC Bartholomew
Feb 16, 2002·Science·Qinghong ZhangRichard H Goodman
Jul 9, 2002·Molecular and Cellular Biology·Jeffrey D Hildebrand, Philippe Soriano
Nov 7, 2002·Molecular Cell·Vivek KumarAneel K Aggarwal
Jan 1, 2003·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·G Chinnadurai
Mar 12, 2003·Proceedings of the National Academy of Sciences of the United States of America·Muhammad Al-HajjMichael F Clarke
Apr 5, 2003·Proceedings of the National Academy of Sciences of the United States of America·Madeleine GrooteclaesSteven M Frisch
May 29, 2003·Molecular Cell·Xia LinXin-Hua Feng
Jul 23, 2003·Nature Structural Biology·Christopher J BarnesRakesh Kumar
Mar 5, 2004·Breast Cancer Research and Treatment·Meghan E MinardGary E Gallick
Sep 6, 2005·Molecular Cell·Yu-Jiang ShiYang Shi
Feb 18, 2006·Trends in Cell Biology·Daniela CordaAlberto Luini
Mar 2, 2006·Molecular and Cellular Biology·Seema PaliwalSteven R Grossman
Apr 7, 2006·Protein Science : a Publication of the Protein Society·Marco NardiniMartino Bolognesi
Jun 3, 2006·Proceedings of the National Academy of Sciences of the United States of America·Qinghong ZhangRichard H Goodman
Jun 20, 2006·Molecular and Cellular Biology·Alexis VergerMerlin Crossley
Sep 21, 2006·The Journal of Biological Chemistry·Su-Yan WangQinghong Zhang
Oct 13, 2006·The EMBO Journal·Shen-Hsi YangAndrew D Sharrocks
Dec 13, 2006·Biochemical and Biophysical Research Communications·Younes AchouriEmile Van Schaftingen
Jun 1, 2007·Molecular Biology of the Cell·René BartzPingsheng Liu
Jan 24, 2009·Proceedings of the National Academy of Sciences of the United States of America·Shuzhen ChenYang Shi
Jun 3, 2009·The Journal of Clinical Investigation·Raghu Kalluri, Robert A Weinberg
Oct 3, 2009·Cell Death and Differentiation·R C KoviS R Grossman
Apr 7, 2010·Journal of Molecular Biology·Jacqueline C MerrillDavid Wotton

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Citations

Sep 11, 2020·Journal of Cellular and Molecular Medicine·Zhenxing WangFengwu Lin
Sep 11, 2018·Oncotarget·Ayesha T ChawlaSteven R Grossman
Apr 26, 2020·Cell Death & Disease·Boxiao DingSteven R Grossman
Jun 20, 2019·Journal of Cell Communication and Signaling·Pengyun WangShu Zhou
Jan 26, 2021·Frontiers in Cell and Developmental Biology·Catarina Serra-AlmeidaLiliana Bernardino
Feb 2, 2021·The Journal of Biological Chemistry·Jeffry C NicholsWilliam E Royer
Feb 27, 2020·Cell Reports·Swapnil S ParhadWilliam E Theurkauf
Dec 3, 2020·Structure·Anne M JecroisWilliam E Royer
May 1, 2021·Cells·Yingnan ZhangYongqing Liu
May 12, 2021·Scientific Reports·Bartolomeus J MeijerJarom Heijmans
Jul 23, 2021·The Journal of Investigative Dermatology·Hong LiMingxia Huang
Aug 6, 2021·Cell Death Discovery·Chenxi WuLei Xue
Jul 2, 2021·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Zhi Chen

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Methods Mentioned

BETA
pull-down
pulldown
X-ray
histone acetylation
ubiquitination
ChIP-seq
PCR
xenografts
immunoprecipitation

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