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.
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China; The Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng, China.
authors.forename: Fujun
authors.initials: F
authors.lastname: Dai
authors.forename: Yihua
authors.initials: Y
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Huang
authors.forename: Jinhua
authors.initials: J
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.forename: Jingjie
authors.initials: J
authors.lastname: Li
authors.forename: Weiguang
authors.initials: W
authors.lastname: Tong
authors.forename: Mingyao
authors.initials: M
authors.lastname: Liu
authors.forename: Zhengfang
authors.initials: Z
authors.lastname: Yi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D015398:Signal Transduction / Q000187:drug effects*; D054852:Small Molecule Libraries / Q000494:pharmacology*
chemical_list: D054852:Small Molecule Libraries; D051416:Focal Adhesion Protein-Tyrosine Kinases
keywords: FAK pathway; colorectal tumour; metastasis; small molecule