Laboratory of Translational Therapeutics, Korea Research Institute of Chemical Technology, Yuseong-Gu, Taejon, 305-600, Korea.
Mol Cell Biochem. 2014 Apr;389(1-2):69-77. doi: 10.1007/s11010-013-1928-8. Epub 2013 Dec 24.
Migration and invasion comprise key steps in cancer metastasis. Through the migration and invasion into and out of lymphatic and/or blood vessels, cancer cells can be spread out into the tissues in remote site from the origin. Degradation of extracellular matrix (ECM) must be preceded prior to the metastasis of cancer cells. Matrix metalloproteinases (MMP) can degrade ECM, thus allow cells to migrate from the original site. Among MMPs, two gelatinase MMP-2 and MMP-9 play particularly important roles in ECM degradation. Here, we report that recently developed p21-activated kinase 4 inhibitor PF-3758309 shows anti-metastatic effect in A549 human lung cancer cell. PF-3758309 suppresses CREB, NF-κB, and β-catenin pathways, which are well known to be closely related with cell migration. This leads to the downregulation of MMP-2/MMP-9 expressions and the inhibition of A549 lung cancer metastasis.
迁移和侵袭是癌症转移的关键步骤。通过迁移和侵袭淋巴和/或血管，癌细胞可以从起源部位扩散到远处的组织中。在癌细胞转移之前，必须先降解细胞外基质（ECM）。基质金属蛋白酶（MMP）可以降解 ECM，从而允许细胞从原始部位迁移。在 MMP 中，两种明胶酶 MMP-2 和 MMP-9 在 ECM 降解中起着特别重要的作用。在这里，我们报告最近开发的 p21 激活激酶 4 抑制剂 PF-3758309 在人肺癌 A549 细胞中显示出抗转移作用。PF-3758309 抑制 CREB、NF-κB 和 β-连环蛋白途径，这些途径与细胞迁移密切相关。这导致 MMP-2/MMP-9 表达的下调和 A549 肺癌转移的抑制。
