LEM domain containing 1 promotes oral squamous cell carcinoma invasion and endothelial transmigration.

LEM domain containing 1 promotes oral squamous cell carcinoma invasion and endothelial transmigration.
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DOI:
10.1038/bjc.2016.167
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发表时间:
2016-06-28
影响因子:
8.8
通讯作者:
Kuniyasu H
Kuniyasu H
中科院分区:
医学1区
文献类型:
--
作者:
Sasahira T;Kurihara M;Nakashima C;Kirita T;Kuniyasu H

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口腔鳞状细胞癌具有较高的局部侵袭和淋巴结转移潜能。因此,早期发现和阐明口腔鳞状细胞癌的详细分子机制是重要的。LEM结构域包含1(LEMD1)是一种新的肿瘤-睾丸抗原,其在口腔鳞状细胞癌中的作用尚不清楚。我们对289例口腔鳞癌患者进行了LEMD1的免疫组织化学分析,并检测了LEMD1在口腔鳞癌中的功能。免疫组织化学分析显示,101例患者LEMD1阳性。口腔鳞状细胞癌中LEM结构域包含1的表达水平与肿瘤进展(T因子和临床分期)、淋巴结转移和预后不良显著相关。包含1表达的LEM结构域是口腔鳞癌患者无病生存的独立预测因子。在口腔鳞状细胞癌中,LEMD1基因敲除抑制了癌细胞的侵袭。此外,下调LEMD1表达可抑制口腔鳞状细胞癌与血管或淋巴管内皮细胞的黏附和迁移。我们的发现表明,LEMD1是一种新的肿瘤进展因子,可能是口腔鳞状细胞癌有用的诊断和治疗靶点。
Oral squamous cell carcinomas have high potential for locoregional invasion and nodal metastasis. Thus, early detection and elucidation of detailed molecular mechanisms of OSCCs are important. Roles of LEM domain containing 1 (LEMD1), a novel cancer–testis antigen, in OSCCs are unclear. We performed immunohistochemical analysis of LEMD1 in 289 OSCC patients and examined functions of LEMD1 in these carcinomas. Immunohistochemical analysis showed that 101 patients were positive for LEMD1. LEM domain containing 1 expression levels in OSCCs significantly correlated with tumour progression (T factor and clinical stage), nodal metastasis, and poor prognosis. LEM domain containing 1 expression was an independent predictor of disease-free survival in OSCC patients. In OSCCs, LEMD1 knockdown suppressed cancer cell invasion. Moreover, downregulation of LEMD1 expression inhibited adhesion and transmigration of OSCCs and vascular or lymphatic vascular endothelial cells. Our findings suggest that LEMD1 is a novel tumour progressive factor and may be a useful diagnostic and therapeutic target in OSCCs.