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Targeting Gli Transcription Activation by Small Molecule Suppresses Tumor Growth

Targeted inhibition of Hedgehog signaling at the cell membrane has been associated with anti-cancer activity in preclinical and early clinical studies. Hedgehog signaling involves activation of Gli transcription factors that can also be induced by alternative pathways. In this study we identified an...

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Autores principales: Bosco-Clément, Geneviève, Zhang, Fang, Chen, Zhao, Zhou, Hai-Meng, Li, Hui, Mikami, Iwao, Hirata, Tomomi, Yagui-Beltran, Adam, Lui, Natalie, Do, Hanh T., Cheng, Tiffany, Tseng, Hsin-Hui, Choi, Helen, Fang, Li-Tai, Kim, Il-Jin, Yue, Dongsheng, Wang, Changli, Zheng, Qingfeng, Fujii, Naoaki, Mann, Michael, Jablons, David M., He, Biao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3947751/
https://www.ncbi.nlm.nih.gov/pubmed/23686308
http://dx.doi.org/10.1038/onc.2013.164
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author Bosco-Clément, Geneviève
Zhang, Fang
Chen, Zhao
Zhou, Hai-Meng
Li, Hui
Mikami, Iwao
Hirata, Tomomi
Yagui-Beltran, Adam
Lui, Natalie
Do, Hanh T.
Cheng, Tiffany
Tseng, Hsin-Hui
Choi, Helen
Fang, Li-Tai
Kim, Il-Jin
Yue, Dongsheng
Wang, Changli
Zheng, Qingfeng
Fujii, Naoaki
Mann, Michael
Jablons, David M.
He, Biao
author_facet Bosco-Clément, Geneviève
Zhang, Fang
Chen, Zhao
Zhou, Hai-Meng
Li, Hui
Mikami, Iwao
Hirata, Tomomi
Yagui-Beltran, Adam
Lui, Natalie
Do, Hanh T.
Cheng, Tiffany
Tseng, Hsin-Hui
Choi, Helen
Fang, Li-Tai
Kim, Il-Jin
Yue, Dongsheng
Wang, Changli
Zheng, Qingfeng
Fujii, Naoaki
Mann, Michael
Jablons, David M.
He, Biao
author_sort Bosco-Clément, Geneviève
collection PubMed
description Targeted inhibition of Hedgehog signaling at the cell membrane has been associated with anti-cancer activity in preclinical and early clinical studies. Hedgehog signaling involves activation of Gli transcription factors that can also be induced by alternative pathways. In this study we identified an interaction between Gli proteins and a transcription co-activator TAF9, and validated its functional relevance in regulating Gli transactivation. We also describe a novel, synthetic small molecule, FN1-8, that efficiently interferes with Gli/TAF9 interaction and down-regulate Gli/TAF9 dependent transcriptional activity. More importantly, FN1-8 suppresses cancer cell proliferation in vitro and inhibits tumor growth in vivo. Our results suggest that blocking Gli transactivation, a key control point of multiple oncogenic pathways, may be an effective anti-cancer strategy.
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spelling pubmed-39477512014-10-17 Targeting Gli Transcription Activation by Small Molecule Suppresses Tumor Growth Bosco-Clément, Geneviève Zhang, Fang Chen, Zhao Zhou, Hai-Meng Li, Hui Mikami, Iwao Hirata, Tomomi Yagui-Beltran, Adam Lui, Natalie Do, Hanh T. Cheng, Tiffany Tseng, Hsin-Hui Choi, Helen Fang, Li-Tai Kim, Il-Jin Yue, Dongsheng Wang, Changli Zheng, Qingfeng Fujii, Naoaki Mann, Michael Jablons, David M. He, Biao Oncogene Article Targeted inhibition of Hedgehog signaling at the cell membrane has been associated with anti-cancer activity in preclinical and early clinical studies. Hedgehog signaling involves activation of Gli transcription factors that can also be induced by alternative pathways. In this study we identified an interaction between Gli proteins and a transcription co-activator TAF9, and validated its functional relevance in regulating Gli transactivation. We also describe a novel, synthetic small molecule, FN1-8, that efficiently interferes with Gli/TAF9 interaction and down-regulate Gli/TAF9 dependent transcriptional activity. More importantly, FN1-8 suppresses cancer cell proliferation in vitro and inhibits tumor growth in vivo. Our results suggest that blocking Gli transactivation, a key control point of multiple oncogenic pathways, may be an effective anti-cancer strategy. 2013-05-20 2014-04-17 /pmc/articles/PMC3947751/ /pubmed/23686308 http://dx.doi.org/10.1038/onc.2013.164 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Bosco-Clément, Geneviève
Zhang, Fang
Chen, Zhao
Zhou, Hai-Meng
Li, Hui
Mikami, Iwao
Hirata, Tomomi
Yagui-Beltran, Adam
Lui, Natalie
Do, Hanh T.
Cheng, Tiffany
Tseng, Hsin-Hui
Choi, Helen
Fang, Li-Tai
Kim, Il-Jin
Yue, Dongsheng
Wang, Changli
Zheng, Qingfeng
Fujii, Naoaki
Mann, Michael
Jablons, David M.
He, Biao
Targeting Gli Transcription Activation by Small Molecule Suppresses Tumor Growth
title Targeting Gli Transcription Activation by Small Molecule Suppresses Tumor Growth
title_full Targeting Gli Transcription Activation by Small Molecule Suppresses Tumor Growth
title_fullStr Targeting Gli Transcription Activation by Small Molecule Suppresses Tumor Growth
title_full_unstemmed Targeting Gli Transcription Activation by Small Molecule Suppresses Tumor Growth
title_short Targeting Gli Transcription Activation by Small Molecule Suppresses Tumor Growth
title_sort targeting gli transcription activation by small molecule suppresses tumor growth
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3947751/
https://www.ncbi.nlm.nih.gov/pubmed/23686308
http://dx.doi.org/10.1038/onc.2013.164
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