MMP1 promotes tumor growth and metastasis in esophageal squamous cell carcinoma
MMP1 promotes tumor growth and metastasis in esophageal squamous cell carcinoma
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MMP1促进食管鳞癌肿瘤生长和转移
DOI：
10.1016/j.canlet.2016.04.034
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发表时间：
2016-07-10
期刊：
影响因子：
9.7
通讯作者：
Yang, Hong
中科院分区：
文献类型：
--
作者：
Liu, Min;Hu, Yi;Yang, Hong
基质金属蛋白酶在食管鳞状细胞癌（ESCC）的发生发展中起重要作用。在这里，我们发现，MMP 1的表达显着增加，在大多数食管鳞癌与非肿瘤组织相比。MMP 1高表达与淋巴结转移、微血管密度及TNM分期密切相关。Kaplan-Meier和多变量分析表明MMP 1是两个独立队列613例ESCC患者总生存率的独立因素。体外研究表明，MMP 1过表达可增强细胞活力、集落形成能力和细胞迁移能力。而MMP 1的敲低则导致相反的现象。体内实验结果表明，MMP 1的异位表达促进了肿瘤的生长和转移。进一步的研究表明MMP 1通过激活PI 3 K/AKT通路促进ESCC的发生。LY 294002对PI 3 K/AKT通路的抑制显著减弱MMP 1介导的细胞增殖和迁移。综上所述，我们的数据表明，MMP 1作为一个癌基因的功能，并作为一个预后的生物标志物和潜在的治疗ESCC的目标。(C)2016爱思唯尔爱尔兰有限公司版权所有。
Matrix metalloproteinases play an essential role in the progression of esophageal squamous cell carcinoma (ESCC). Here, we show that MMP1 expression was markedly increased in a majority of ESCC compared with nontumorous tissue. High expressions of MMP1 were closely associated with lymph node metastasis, microvessel density and advanced TNM stage. Kaplan-Meier and multivariate analyses indicated MMP1 as an independent factor for overall survival in two independent cohorts of 613 patients with ESCC. In vitro studies demonstrated that MMP1 overexpression resulted in enhanced cell viability, abilities of colony formation and cell migration. The knockdown of MMP1 in ESCC cells resulted in the opposite phenomenon. Consistently, in vivo data showed that ectopic expression of MMP1 promoted tumor growth and metastasis. Further study revealed that MMP1 facilitated ESCC through the activation of the PI3K/AKT pathway. Inhibition of the PI3K/AKT pathway by LY294002 significantly attenuated MMP1-mediated cell proliferation and migration. Taken together, our data suggest that MMP1 functions as an oncogene and serves as a prognostic biomarker and a potential therapeutic target in ESCC. (C) 2016 Elsevier Ireland Ltd. All rights reserved.