Testes-specific protease 50 promotes cell invasion and metastasis by increasing NF-kappaB-dependent matrix metalloproteinase-9 expression.
Testes-specific protease 50 promotes cell invasion and metastasis by increasing NF-kappaB-dependent matrix metalloproteinase-9 expression.
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睾丸特异性蛋白酶 50 通过增加 NF-κB 依赖性基质金属蛋白酶 9 的表达来促进细胞侵袭和转移
DOI：
10.1038/cddis.2015.61
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发表时间：
2015-03-26
影响因子：
9
通讯作者：
中科院分区：
文献类型：
--
作者：
乳腺癌的高死亡率通常与患者的转移进展有关。以前我们已经证明，睾丸特异性蛋白酶50 (TSP50)，乳腺癌样本中过度表达的致癌基因，可以促进细胞增殖和肿瘤发生。然而，TSP50是否在细胞侵袭和肿瘤转移中也起关键作用，其机制尚不清楚。本研究发现，TSP50过表达可显著促进体外三维培养系统中细胞的迁移、侵袭、粘附和星状结构的形成以及体内肺转移。相反，TSP50敲低引起相反的变化。机制研究表明，TSP50诱导的细胞迁移和转移需要NF-κB信号通路，进一步的结果表明，TSP50过表达增强了NF-κB信号传导靶基因MMP9的表达和分泌。此外，敲低MMP9可抑制细胞在体外的迁移和侵袭以及体内的肺转移。最重要的是，人类乳腺癌样本的免疫组化染色强烈显示TSP50和p65以及TSP50和MMP9的共表达与转移增加和生存差相关。此外，我们发现一些乳腺癌诊断相关的特征，如肿瘤大小、肿瘤分级、雌激素受体（ER）和孕激素受体（PR）水平，与TSP50/p65和TSP50/MMP9的表达状态密切相关。综上所述，这项工作确定了TSP50激活MMP9是人类乳腺癌侵袭和转移的一种新的信号机制。
The high mortality in breast cancer is often associated with metastatic progression in patients. Previously we have demonstrated that testes-specific protease 50 (TSP50), an oncogene overexpressed in breast cancer samples, could promote cell proliferation and tumorigenesis. However, whether TSP50 also has a key role in cell invasion and cancer metastasis, and the mechanism underlying the process are still unclear. Here we found that TSP50 overexpression greatly promoted cell migration, invasion, adhesion and formation of the stellate structures in 3D culture system in vitro as well as lung metastasis in vivo. Conversely, TSP50 knockdown caused the opposite changes. Mechanistic studies revealed that NF-κB signaling pathway was required for TSP50-induced cell migration and metastasis, and further results indicated that TSP50 overexpression enhanced expression and secretion of MMP9, a target gene of NF-κB signaling. In addition, knockdown of MMP9 resulted in inhibition of cell migration and invasion in vitro and lung metastasis in vivo. Most importantly, immunohistochemical staining of human breast cancer samples strongly showed that the coexpression of TSP50 and p65 as well as TSP50 and MMP9 were correlated with increased metastasis and poor survival. Furthermore, we found that some breast cancer diagnosis-associated features such as tumor size, tumor grade, estrogen receptors (ER) and progesterone receptors (PR) levels, were correlated well with TSP50/p65 and TSP50/MMP9 expression status. Taken together, this work identified the TSP50 activation of MMP9 as a novel signaling mechanism underlying human breast cancer invasion and metastasis.
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影响因子：
56.9
作者：
Cukierman, E;Pankov, R;Yamada, KM
通讯作者：
Yamada, KM
DOI：
10.1016/s0006-291x(02)00350-9
发表时间：
2002-05-17
影响因子：
3.1
作者：
Liu, JF;Crépin, M;Ledoux, D
通讯作者：
Ledoux, D
影响因子：
64.5
作者：
Hotary, KB;Allen, ED;Weiss, SJ
通讯作者：
Weiss, SJ
影响因子：
5.1
作者：
Lee, Eun-Jung;Kim, So-Young;Kim, Hee-Sun
通讯作者：
Kim, Hee-Sun
影响因子：
4.8
作者：
Hong, S;Park, KK;Chang, YC
通讯作者：
Chang, YC