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A novel synthetic small molecule YH-306 suppresses colorectal tumour growth and metastasis viaFAK pathway

Cell migration and invasion are key processes in the metastasis of cancer, and suppression of these steps is a promising strategy for cancer therapeutics. The aim of this study was to explore small molecules for treating colorectal cancer (CRC) and to investigate their anti-metastatic mechanisms. In...

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Autores principales: Dai, Fujun, Chen, Yihua, Huang, Li, Wang, Jinhua, Zhang, Tao, Li, Jingjie, Tong, Weiguang, Liu, Mingyao, Yi, Zhengfang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BlackWell Publishing Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4407606/
https://www.ncbi.nlm.nih.gov/pubmed/25351103
http://dx.doi.org/10.1111/jcmm.12450
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author Dai, Fujun
Chen, Yihua
Huang, Li
Wang, Jinhua
Zhang, Tao
Li, Jingjie
Tong, Weiguang
Liu, Mingyao
Yi, Zhengfang
author_facet Dai, Fujun
Chen, Yihua
Huang, Li
Wang, Jinhua
Zhang, Tao
Li, Jingjie
Tong, Weiguang
Liu, Mingyao
Yi, Zhengfang
author_sort Dai, Fujun
collection PubMed
description Cell migration and invasion are key processes in the metastasis of cancer, and suppression of these steps is a promising strategy for cancer therapeutics. The aim of this study was to explore small molecules for treating colorectal cancer (CRC) and to investigate their anti-metastatic mechanisms. In this study, six CRC cell lines were used. We showed that YH-306 significantly inhibited the migration and invasion of CRC cells in a dose-dependent manner. In addition, YH-306 inhibited cell adhesion and protrusion formation of HCT116 and HT-29 CRC cells. Moreover, YH-306 potently suppressed uninhibited proliferation in all six CRC cell lines tested and induced cell apoptosis in four cell lines. Furthermore, YH-306 inhibited CRC colonization in vitro and suppressed CRC growth in a xenograft mouse model, as well as hepatic/pulmonary metastasis in vivo. YH-306 suppressed the activation of focal adhesion kinase (FAK), c-Src, paxillin, and phosphatidylinositol 3-kinases (PI3K), Rac1 and the expression of matrix metalloproteases (MMP) 2 and MMP9. Meanwhile, YH-306 also inhibited actin-related protein (Arp2/3) complex-mediated actin polymerization. Taken together, YH-306 is a candidate drug in preventing growth and metastasis of CRC by modulating FAK signalling pathway.
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spelling pubmed-44076062015-04-23 A novel synthetic small molecule YH-306 suppresses colorectal tumour growth and metastasis viaFAK pathway Dai, Fujun Chen, Yihua Huang, Li Wang, Jinhua Zhang, Tao Li, Jingjie Tong, Weiguang Liu, Mingyao Yi, Zhengfang J Cell Mol Med Original Articles Cell migration and invasion are key processes in the metastasis of cancer, and suppression of these steps is a promising strategy for cancer therapeutics. The aim of this study was to explore small molecules for treating colorectal cancer (CRC) and to investigate their anti-metastatic mechanisms. In this study, six CRC cell lines were used. We showed that YH-306 significantly inhibited the migration and invasion of CRC cells in a dose-dependent manner. In addition, YH-306 inhibited cell adhesion and protrusion formation of HCT116 and HT-29 CRC cells. Moreover, YH-306 potently suppressed uninhibited proliferation in all six CRC cell lines tested and induced cell apoptosis in four cell lines. Furthermore, YH-306 inhibited CRC colonization in vitro and suppressed CRC growth in a xenograft mouse model, as well as hepatic/pulmonary metastasis in vivo. YH-306 suppressed the activation of focal adhesion kinase (FAK), c-Src, paxillin, and phosphatidylinositol 3-kinases (PI3K), Rac1 and the expression of matrix metalloproteases (MMP) 2 and MMP9. Meanwhile, YH-306 also inhibited actin-related protein (Arp2/3) complex-mediated actin polymerization. Taken together, YH-306 is a candidate drug in preventing growth and metastasis of CRC by modulating FAK signalling pathway. BlackWell Publishing Ltd 2015-02 2014-10-29 /pmc/articles/PMC4407606/ /pubmed/25351103 http://dx.doi.org/10.1111/jcmm.12450 Text en © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. http://creativecommons.org/licenses/by/3.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Dai, Fujun
Chen, Yihua
Huang, Li
Wang, Jinhua
Zhang, Tao
Li, Jingjie
Tong, Weiguang
Liu, Mingyao
Yi, Zhengfang
A novel synthetic small molecule YH-306 suppresses colorectal tumour growth and metastasis viaFAK pathway
title A novel synthetic small molecule YH-306 suppresses colorectal tumour growth and metastasis viaFAK pathway
title_full A novel synthetic small molecule YH-306 suppresses colorectal tumour growth and metastasis viaFAK pathway
title_fullStr A novel synthetic small molecule YH-306 suppresses colorectal tumour growth and metastasis viaFAK pathway
title_full_unstemmed A novel synthetic small molecule YH-306 suppresses colorectal tumour growth and metastasis viaFAK pathway
title_short A novel synthetic small molecule YH-306 suppresses colorectal tumour growth and metastasis viaFAK pathway
title_sort novel synthetic small molecule yh-306 suppresses colorectal tumour growth and metastasis viafak pathway
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4407606/
https://www.ncbi.nlm.nih.gov/pubmed/25351103
http://dx.doi.org/10.1111/jcmm.12450
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