Specific blockade of the ERK pathway inhibits the invasiveness of tumor cells: down-regulation of matrix metalloproteinase-3/-9/-14 and CD44
Specific blockade of the ERK pathway inhibits the invasiveness of tumor cells: down-regulation of matrix metalloproteinase-3/-9/-14 and CD44
复制标题
DOI：
10.1016/s0006-291x(03)00670-3
复制
发表时间：
2003-05-16
影响因子：
3.1
通讯作者：
Kohno, M
中科院分区：
文献类型：
--
作者：
Tanimura, S;Asato, K;Kohno, M
基质金属蛋白酶（MMPs）的高表达与许多肿瘤细胞转移潜能的增加有关。由于ERK通路的激活与MMP-9的表达有关，我们研究了ERK激活、MMP-9表达和人肿瘤细胞侵袭性表型之间可能的相关性。肿瘤细胞中ERK通路的激活状态与侵袭表型密切相关，侵袭表型由细胞通过重建的细胞外基质侵袭的能力决定。在检测到ERK通路组成性激活的肿瘤细胞中观察到MMP-9以及MMP-3、MMP-14和CD 44的表达升高。PD 184352是一种特异性的、强效的丝裂原活化蛋白激酶（MAP）/ERK激酶（MEK）抑制剂，阻断ERK通路可抑制MMP-3、MMP-9、MMP-14的表达。和CD 44的表达，并显著抑制肿瘤细胞的侵袭能力。这些结果意味着，除了抗增殖作用之外，ERK途径的特异性阻断预期在肿瘤细胞中产生抗转移作用。(C)2003 Elsevier Science（美国）。All rights reserved.
Elevated expression of matrix metalloproteinases (MMPs) is associated with increased metastatic potential in many tumor cells. As activation of the ERK pathway has been linked to the expression of MMP-9, we examined a possible correlation between ERK activation, MMP-9 expression, and invasive phenotype in human tumor cells. Activation state of the ERK pathway in tumor cells was well correlated with the invasive phenotype, which was determined by the ability of cells to invade through reconstituted extracellular matrix. Elevated expression of MMP-9 as well as of MMP-3, MMP-14, and CD44 was observed in tumor cells in which constitutive activation of the ERK pathway is detected. Blockade of the ERK pathway by treatment with PD184352, a specific and powerful inhibitor of mitogen-activated protein (MAP) kinase/ERK kinase (MEK), suppressed the expression of MMP-3, MMP-9, MMP-14. and CD44, and inhibited markedly the invasiveness of tumor cells. These results imply that, in addition to anti-proliferative effects, specific blockade of the ERK pathway is expected to result in anti-metastatic effects in tumor cells. (C) 2003 Elsevier Science (USA). All rights reserved.