TY - JOUR T1 - Targeting the Metastasis Suppressor, N-Myc Downstream Regulated Gene-1 (NDRG1), with Novel Di-2-Pyridylketone Thiosemicarbazones: Suppression of Tumor Cell Migration and Cell-Collagen Adhesion by Inhibiting FAK/Paxillin Signaling JF - Molecular Pharmacology JO - Mol Pharmacol DO - 10.1124/mol.115.103044 SP - mol.115.103044 AU - Xiongzhi Wangpu AU - Jiaoyang Lu AU - Ruxing Xi AU - Fei Yue AU - Sumit Sahni AU - Kyung Chan Park AU - Sharleen Menezes AU - Michael Huang AU - Minhua Zheng AU - Zaklina Kovacevic AU - Des R. Richardson Y1 - 2016/01/01 UR - http://molpharm.aspetjournals.org/content/early/2016/02/19/mol.115.103044.abstract N2 - Metastasis is a complex process that is regulated by multiple signaling pathways, with the FAK/paxillin pathway playing a major role in the formation of focal adhesions and cell motility. NDRG1 is a potent metastasis suppressor in many solid tumor types, including prostate and colon cancer. Considering the anti-metastatic effect of NDRG1 and the crucial involvement of the FAK/paxillin pathway in cellular migration and cell-matrix adhesion, we assessed the effects of NDRG1 on this important oncogenic pathway. In the present study, NDRG1 over-expression and silencing models of HT29 colon cancer and DU145 prostate cancer cells were utilized to examine the activation of FAK/paxillin signaling and the formation of focal adhesions. The expression of NDRG1 resulted in a marked and significant decrease in the activating phosphorylation of FAK and paxillin, while silencing of NDRG1 resulted in an opposite effect. The expression of NDRG1 also inhibited the formation of focal adhesions as well as cell migration and cell-collagen adhesion. Incubation of cells with novel thiosemicarbazones, namely Dp44mT and DpC, that up-regulate NDRG1, also resulted in decreased phosphorylation of FAK and paxillin. The ability of these thiosemicarbazones to inhibit cell migration and metastasis could be mediated, at least in part, through the FAK/paxillin pathway. ER -