MTUS1/ATIP3a down-regulation is associated with enhanced migration, invasion and poor prognosis in salivary adenoid cystic carcinoma.
MTUS1/ATIP3a down-regulation is associated with enhanced migration, invasion and poor prognosis in salivary adenoid cystic carcinoma.
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MTUS1/ATIP3a 下调与唾液腺腺样囊性癌的迁移、侵袭增强和不良预后相关。
DOI：
10.1186/s12885-015-1209-x
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发表时间：
2015-03-31
期刊：
影响因子：
3.8
通讯作者：
Wang A
中科院分区：
文献类型：
--
作者：
Zhao T;Ding X;Chang B;Zhou X;Wang A
微管相关抑癌基因（MTUS 1）已被证实是多种恶性肿瘤的抑癌基因。在这项研究中，我们研究了MTUS 1在涎腺腺样囊性癌（SACC）的发展中的作用及其对SACC迁移和侵袭的功能影响。通过免疫组化检测包括49例原发性SACC在内的存档临床样本的MTUS 1表达。进行统计学分析以评估MTUS 1与组织病理学特征和存活率之间的相关性。MTUS 1/ATIP（AT 2受体相互作用蛋白）亚型的表达在SACC组织样品和细胞系中使用定量RT-PCR测定。然后通过体外细胞迁移和侵袭实验研究MTUS 1/ATIP 3a是否介导SACC的迁移和侵袭。我们证实MTUS 1的下调是SACC中的常见事件，并且与远处转移相关，并且与总生存率和无病生存率降低相关。亚型特异性定量RT-PCR分析显示ATIP 1、ATIP 3a和ATIP 3b是SACC中MTUS 1基因产物的主要亚型，并且与匹配的正常组织相比，在SACC中显著下调。对于功能分析，我们发现SACC-LM细胞（具有较高迁移和侵袭能力的SACC细胞系）与SACC-83细胞（较低迁移和侵袭能力）相比具有较低的ATIP 3a表达水平。SACC-LM细胞中ATIP 3a表达的恢复诱导了抗增殖活性并抑制了迁移和侵袭能力。ATIP 3a基因的敲除可促进SACC-83细胞的增殖、迁移和侵袭能力。ATIP 3a的恢复可抑制SACC-LM细胞中ERK 1/2的磷酸化、Slug和Vimentin的表达，而ATIP 3a的敲除可增加SACC-83细胞中ERK 1/2的磷酸化、Slug和Vimentin的表达。我们的研究证实，MTUS 1在SACC的进展中起着重要作用，并可能作为SACC患者的生物标志物或治疗靶点。MTUS 1/ATIP 3a的下调有助于SACC的增殖、迁移和侵袭能力。本文的在线版本（doi：10.1186/s12885-015-1209-x）包含补充材料，可供授权用户使用。
Microtubule-associated tumor suppressor gene (MTUS1) has been identified as tumor suppressor gene in many malignant tumors. In this study, we investigated the role of MTUS1 in the development of salivary adenoid cystic carcinoma (SACC) and its functional effect on the migration and invasion of SACC. Archival clinical samples including 49 primary SACC were examined for MTUS1 expression by immunohistochemistry. Statistical analyses were performed to evaluate the correlation between MTUS1 with histopathological features and survival. The expression of MTUS1/ATIP (AT2 receptor-interacting protein) isoforms was determined in SACC tissue samples and cell lines using quantitative RT-PCR assays. Then we investigated whether the migration and invasion of SACC were mediated by MTUS1/ATIP3a using in vitro cell migration and invasion assay. We confirmed that the down-regulation of MTUS1 was a frequent event in SACC, and was correlated with distant metastasis and associated with reduced overall survival and disease free survival. Isoform specific quantitative RT-PCR assays revealed that ATIP1, ATIP3a and ATIP3b were the major isoforms of the MTUS1 gene products in SACC, and were significant down-regulation in SACC as compared to matching normal tissues. For functional analyses, we found that SACC-LM cells (SACC cell line with higher migration and invasion ability) possessed a lower expression level of ATIP3a compared to SACC-83 cells (lower migration and invasion ability). Restoration of ATIP3a expression in SACC-LM cells induced anti-proliferative activity and inhibited the migration and invasion ability. Knockdown of ATIP3a promoted the proliferation, migration and invasion ability of SACC-83 cells. Restoration of ATIP3a inhibited the phosphorylation of ERK (extracellular-regulated kinase) 1/2, the expression of Slug and Vimentin in SACC-LM cells, while knockdown of ATIP3a increased the phosphorylation of ERK1/2, the expression of Slug and Vimentin in SACC-83 cells. Our studies confirm that MTUS1 plays an important role in the progression of SACC, and may serve as a biomarker or therapeutic target for patients with SACC. MTUS1/ATIP3a down-regulation contributes to the proliferation, migration and the invasion abilities of SACC. The online version of this article (doi:10.1186/s12885-015-1209-x) contains supplementary material, which is available to authorized users.
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影响因子：
3.8
作者：
Rogler A;Hoja S;Giedl J;Ekici AB;Wach S;Taubert H;Goebell PJ;Wullich B;Stöckle M;Lehmann J;Petsch S;Hartmann A;Stoehr R
通讯作者：
Stoehr R
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影响因子：
3.3
作者：
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通讯作者：
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影响因子：
4
作者：
Joseph, Mathew J.;Dangi-Garimella, Surabbi;Munshi, Hidayatullah G.
通讯作者：
Munshi, Hidayatullah G.
影响因子：
6.6
作者：
Ding X;Zhang N;Cai Y;Li S;Zheng C;Jin Y;Yu T;Wang A;Zhou X
通讯作者：
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影响因子：
14.9
作者：
Hao L;Xiao-lin N;Qi C;Yi-ping Y;Jia-quan L;Yan-ning L
通讯作者：
Yan-ning L