Targeting the Metastasis Suppressor, N-Myc Downstream Regulated Gene-1, with Novel Di-2-Pyridylketone Thiosemicarbazones: Suppression of Tumor Cell Migration and Cell-Collagen Adhesion by Inhibiting Focal Adhesion Kinase/Paxillin Signaling

• DOI: 10.1124/mol.115.103044
• Publication Date: 2016-02-20T03:14:02Z
• Authors: Xiongzhi Wangpu; Jiaoyang Lu; Ruxing Xi; Fei Yue; Sumit Sahni; Kyung Chan Park; Sharleen Menezes; Michael L.H. Huang; Minhua Zheng; Zaklina Kovacevic; Des R. Richardson
• Keywords: Paxillin; PTK2; DU145

Metastasis is a complex process that regulated by multiple signaling pathways, with the focal adhesion kinase (FAK)/paxillin pathway playing major role in formation of adhesions and cell motility. N-myc downstream gene-1 (NDRG1) potent metastasis suppressor many solid tumor types, including prostate colon cancer. Considering antimetastatic effect NDRG1 crucial involvement FAK/paxillin cellular migration cell-matrix adhesion, we assessed effects on this important oncogenic pathway. In present study, overexpression silencing models HT29 cancer DU145 cells were used to examine activation adhesions. The expression resulted marked significant decrease activating phosphorylation FAK paxillin, whereas an opposite effect. also inhibited as well cell-collagen adhesion. Incubation novel thiosemicarbazones, namely di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone 4-cyclohexyl-4-methyl-3-thiosemicarbazone, upregulate decreased paxillin. ability these thiosemicarbazones inhibit could be mediated, at least part, through