A Fra-1-dependent, matrix metalloproteinase driven EGFR activation promotes human lung epithelial cell motility and invasion.

Adiseshaiah P; Vaz M; Machireddy NKalvakolanu DVReddy SP

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A Fra-1-dependent, matrix metalloproteinase driven EGFR activation promotes human lung epithelial cell motility and invasion.

机译：Fra-1-dependent,基质金属蛋白酶驱动的表皮生长因子受体激活促进人类肺上皮细胞的能动性和入侵。

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We and others have shown a persistently high induction of Fra-1 transcription factor (a dimeric partner of AP-1) levels by respiratory carcinogens in pulmonary epithelial cells. Fra-1 is frequently overexpressed in various human tumors and cancer cells. We have recently shown that Fra-1 significantly promotes growth, motility, and invasion of human pulmonary epithelial cells, the precise molecular mechanisms by which this enhancement occurs are unclear. Because matrix metalloproteinases (MMPs) play key roles in wound healing and lung tumor metastasis, we tested the hypothesis that Fra-1 promotes lung epithelial cell motility and invasion via MMP activation. We show here that MMP-9 and MMP-2 activated signaling plays a critical role in regulating Fra-1-induced lung epithelial cell growth and invasion. Ectopic Fra-1 markedly stimulates MMP-2 and MMP-9 mRNA expression. Inhibition of MMP-2 and MMP-9 activity significantly attenuated Fra-1-driven cell motility and invasion. Furthermore, Fra-1 induced EGFR phosphorylation in an MMP-dependent manner, and an EGFR-specific inhibitor was able to block Fra-1-enhanced cell motility and invasion. Taken together, our data suggest that Fra-1 enhances lung cancer epithelial cell motility and invasion by inducing the activity of MMPs, in particular MMP-2 and MMP-9, and EGFR-activated signaling.

机译：我们和其他人显示居高不下诱导Fra-1转录因子(a二聚的伙伴AP-1)水平的呼吸致癌物质在肺上皮细胞。经常在各种人类肿瘤和癌细胞。Fra-1显著促进经济增长,能动性,入侵人类的肺上皮细胞,精确的分子此增强功能发生的机制不清楚。在伤口愈合和肺部肿瘤中起着关键作用转移,我们测试了Fra-1的假设促进肺上皮细胞的能动性和通过MMP激活入侵。MMP-9和MMP-2激活信号至关重要的作用在调节Fra-1-induced肺上皮细胞生长和入侵。Fra-1明显刺激MMP-2 MMP-9信使rna表达式。活动明显减弱Fra-1-driven细胞的能动性和入侵。诱导MMP-dependent EGFR磷酸化方式,和一个EGFR-specific抑制剂阻止Fra-1-enhanced细胞的能动性和入侵。Fra-1提高肺癌上皮细胞能动性和入侵诱导的活动基质金属蛋白酶,特别是MMP-2 MMP-9,EGFR-activated信号。

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来源
《Journal of Cellular Physiology》 |2008年第2期|405-412|共8页
作者
Adiseshaiah P; Vaz M; Machireddy NKalvakolanu DVReddy SP;
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作者单位

Department of Environmental Health Sciences, Bloomberg School of Public Health, Baltimore, Maryland, USA.;

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原文格式 PDF
正文语种英语
中图分类细胞生物学;
关键词
Cell Line; Epithelial Cells; Wound HealingEnzyme Inhibitorsenzyme activationTumoursMatrix MetalloproteinasesCarcinogensCell LocomotionInvasionsLungcell invasionLocomotion;

机译：HealingEnzyme细胞株;上皮细胞;伤口Inhibitorsenzyme activationTumoursMatrixLocomotionInvasionsLungcell invasionLocomotion;

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A Fra-1-dependent, matrix metalloproteinase driven EGFR activation promotes human lung epithelial cell motility and invasion.

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