EGF promotes invasion by PANC-1 cells through Racl/ROS-dependent secretion and activation of MMP-2
EGF promotes invasion by PANC-1 cells through Racl/ROS-dependent secretion and activation of MMP-2
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DOI：
10.1016/j.bbrc.2008.12.080
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发表时间：
2009-02-06
影响因子：
3.1
通讯作者：
Cosen-Binker, Laura I.
中科院分区：
文献类型：
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作者：
Binker, Marcelo G.;Binker-Cosen, Andres A.;Cosen-Binker, Laura I.
癌症转移涉及肿瘤细胞侵入周围组织。组织屏障的重塑取决于肿瘤细胞降解周围胶原基质然后迁移通过基质缺损的能力。表皮生长因子（EGF）通过激活基质金属蛋白酶-2（MMP-2）调节多种肿瘤细胞的侵袭。在本研究中，我们研究了MMP-2的作用和参与EGF促进人胰腺癌细胞PANC-1的侵袭的信号通路。使用特定的抑制剂，我们发现，EGF刺激这些肿瘤细胞诱导分泌和激活的胶原酶MMP-2，这是EGF刺激的基底膜降解和细胞侵袭所必需的。我们的研究结果还表明，EGF受体下游的信号转导事件涉及PI 3 K-和Src-依赖的Rac 1激活，介导NADPH产生的活性氧负责MMP-2的分泌和激活。(c)2008年爱思唯尔公司All rights reserved.
Cancer metastasis involves tumor cells invading the surrounding tissue. Remodeling of tissue barriers depends on the ability of tumor cells to degrade the Surrounding Collagen matrix and then migrate through the matrix defects. Epidermal growth factor (EGF) has been shown to regulate tumor cell invasion through activation of matrix metalloproteinase-2 (MMP-2) in various tumor Cell types. In the present study, we investigated the role of MMP-2 and the signaling pathway involved in EGF-promoted invasion by human pancreatic cancer cells PANC-1. Using specific inhibitors, we found that EGF stimulation of these tumor cells induced secretion and activation of the collagenase MMP-2, which was required for EGF-stimulated basement membrane degradation and cell invasion. Our results also indicate that signaling events downstream of EGF receptor involved PI3K- and Src-dependent activation of Rac1, which mediated the NADPH-generated reactive oxygen species responsible for MMP-2 secretion and activation. (c) 2008 Elsevier Inc. All rights reserved.