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

Fujun Dai; Yihua Chen; Li Huang; Jinhua Wang; Tao Zhang; Jingjie Li; Weiguang Tong; Mingyao Liu; Zhengfang Yi

doi:10.1111/jcmm.12450

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

Fujun Dai
, Yihua Chen
, Li Huang
, Jinhua Wang
, Tao Zhang
, Jingjie Li
, Weiguang Tong
, Mingyao Liu
, Zhengfang Yi^*

^*Corresponding author for this work

School of Life Sciences

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	383-395
Number of pages	13
Journal	Journal of Cellular and Molecular Medicine
Volume	19
Issue number	2
DOIs	https://doi.org/10.1111/jcmm.12450
State	Published - 1 Feb 2015

Keywords

Colorectal tumour
FAK pathway
Metastasis
Small molecule

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1111/jcmm.12450

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title = "A novel synthetic small molecule YH-306 suppresses colorectal tumour growth and metastasis via FAK pathway",

abstract = "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.",

keywords = "Colorectal tumour, FAK pathway, Metastasis, Small molecule",

author = "Fujun Dai and Yihua Chen and Li Huang and Jinhua Wang and Tao Zhang and Jingjie Li and Weiguang Tong and Mingyao Liu and Zhengfang Yi",

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year = "2015",

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T1 - A novel synthetic small molecule YH-306 suppresses colorectal tumour growth and metastasis via FAK pathway

AU - Dai, Fujun

AU - Chen, Yihua

AU - Huang, Li

AU - Wang, Jinhua

AU - Zhang, Tao

AU - Li, Jingjie

AU - Tong, Weiguang

AU - Liu, Mingyao

AU - Yi, Zhengfang

PY - 2015/2/1

Y1 - 2015/2/1

N2 - 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.

AB - 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.

KW - Colorectal tumour

KW - FAK pathway

KW - Metastasis

KW - Small molecule

UR - https://www.scopus.com/pages/publications/84921697135

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DO - 10.1111/jcmm.12450

M3 - 文章

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JO - Journal of Cellular and Molecular Medicine

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ER -

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

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Keywords

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