Protumoral roles of melanoma inhibitory activity 2 in oral squamous cell carcinoma.
Protumoral roles of melanoma inhibitory activity 2 in oral squamous cell carcinoma.
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DOI：
10.1038/bjc.2013.27
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发表时间：
2013-04-16
影响因子：
8.8
通讯作者：
Kuniyasu H
中科院分区：
文献类型：
--
作者：
Kurihara M;Kirita T;Sasahira T;Ohmori H;Matsushima S;Yamamoto K;Bosserhoff AK;Kuniyasu H
研究黑色素瘤抑制活性2(MIA2)在口腔鳞状细胞癌(OSCC)中的作用。用免疫组织化学方法检测MIA2在口腔鳞状细胞癌中的作用，并用表达MIA2的人口腔鳞癌细胞系进行基因敲除实验。MIA2在93例口腔鳞状细胞癌中表达62例(66.7%)，与肿瘤扩张和淋巴结转移有关。黑色素瘤抑制活性2的表达与瘤内淋巴细胞浸润呈负相关。MIA2基因敲除可降低HSC3细胞的侵袭力和抗凋亡存活率。MIA2基因敲除或MIA2抗体去除可增强MOLT-3淋巴细胞对HSC3细胞层的侵袭作用。在HSC3细胞中，Mia2基因敲除降低了血管内皮生长因子(VEGF)、VEGF-C和VEGF-D的表达。VEGF-C和-D的下调分别是通过抑制p38和细胞外信号调节激酶(ERK)1/2而引起的。在HSC3细胞中，黑色素瘤抑制活性2与整合素α4和α5共沉淀。整合素α4基因敲除降低了p38的磷酸化水平，增加了细胞的凋亡率，而整合素α5基因敲除降低了c-jun氨基末端激酶的磷酸化和细胞凋亡率。抑制JNK可减少HSC3细胞的凋亡率。这些发现表明，Mia2的作用可能是基于整合素的多样性和丝裂原激活的蛋白激酶的亚型。
The role of melanoma inhibitory activity 2 (MIA2) was examined in human oral squamous cell carcinoma (OSCC). MIA2 role was examined by immunohistochemistry of human OSCCs and knockdown studies using human 3 OSCC cell lines with MIA2 expression. MIA2 expression was observed in 62 (66.7%) of 93 OSCCs and was associated with tumour expansion and nodal metastasis. Melanoma inhibitory activity 2 expression was inversely correlated with intratumoral infiltration of lymphocytes. Invasion and anti-apoptotic survival were reduced by MIA2 knockdown in HSC3 cells. MOLT-3 lymphocytes infiltrating the HSC3 cell layer was enhanced by MIA2 knockdown or MIA2 depletion with the antibody. In HSC3 cells, MIA2 knockdown decreased the expressions of vascular endothelial growth factor (VEGF), VEGF-C, and VEGF-D. The downregulation of VEGF-C and -D was caused by inhibition of p38 and extracellular signal-regulated kinase (ERK)1/2, respectively. Melanoma inhibitory activity 2 was co-precipitated with integrin α4 andα5 in HSC3 cells. Integrin α4 knockdown decreased p38 phosphorylation and increased apoptosis, whereas integrin α5 knockdown decreased c-Jun N-terminal kinase (JNK) phosphorylation and apoptosis. Inhibition of JNK decreased apoptosis in the HSC3 cells. These findings suggest that the roles of MIA2 might be based on the variety of the integrins and the subtypes of mitogen-activated protein kinase.
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影响因子：
4.8
作者：
Bosserhoff, AK;Moser, M;Hellerbrand, C
通讯作者：
Hellerbrand, C
影响因子：
1.2
作者：
Bosserhoff, AK;Moser, M;Buettner, R
通讯作者：
Buettner, R
影响因子：
2.5
作者：
Kreppel, Matthias;Eich, Hans Theodor;Scheer, Martin
通讯作者：
Scheer, Martin
影响因子：
2.8
作者：
Kuniyasu, H;Yasui, W;Fidler, IJ
通讯作者：
Fidler, IJ
影响因子：
24.5
作者：
Hellerbrand, C.;Amann, T.;Bosserhoff, A-K
通讯作者：
Bosserhoff, A-K