Transport and Golgi organisation protein 1 is a novel tumour progressive factor in oral squamous cell carcinoma

Transport and Golgi organisation protein 1 is a novel tumour progressive factor in oral squamous cell carcinoma
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DOI:
10.1016/j.ejca.2014.05.006
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发表时间:
2014-08-01
影响因子:
8.4
通讯作者:
Kuniyasu, Hiroki
Kuniyasu, Hiroki
中科院分区:
医学1区
文献类型:
--
作者:
Sasahira, Tomonori;Kirita, Tadaaki;Kuniyasu, Hiroki

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运输和高尔基体组织蛋白 1 (TANGO),也称为 MIA3,属于黑色素瘤抑制活性 (MIA) 基因家族。尽管 MIA 是一种癌基因,但 MIA2 和 TANGO 在多种恶性肿瘤中具有肿瘤抑制功能;因此,MIA基因家族在肿瘤中的作用和功能仍存在争议。本文研究了 TANGO 在口腔鳞状细胞癌 (OSCC) 中的作用。我们分析了 TANGO 在人 OSCC 细胞系中的表达和功能。还通过免疫组织化学检查了 171 例原发性 OSCC 中的 TANGO 表达,并统计评估了 TANGO 阳性与血管密度等临床病理参数之间的相关性。通过敲低 OSCC 细胞中的 TANGO,抑制其生长和侵袭并诱导细胞凋亡。 TANGO 敲除可抑制血小板源性生长因子 β 多肽 (PDGFB) 和 Neuropilin2 的活性。在 35.1% (60/171) 的 OSCC 病例中检测到 TANGO 免疫反应性。 TANGO 表达与 OSCC 中的肿瘤进展、淋巴结转移、临床分期以及血管或淋巴管数量密切相关。显示 TANGO 表达的患者的无病生存率明显低于不表达 TANGO 的患者。这些发现表明,TANGO 可能通过上调 OSCC 中的 PDGFB 和 Neuropilin2 来促进血管生成和淋巴管生成。 (C) 2014 Elsevier Ltd. 保留所有权利。
Transport and Golgi organisation protein 1 (TANGO), also known as MIA3, belongs to the melanoma inhibitory activity (MIA) gene family. Although MIA acts as an oncogene, MIA2 and TANGO have a tumour-suppressive function in several malignancies; accordingly, the role and function of the MIA gene family in tumours remain controversial. Here the roles of TANGO were investigated in oral squamous cell carcinoma (OSCC). We analysed expression and function of TANGO in human OSCC cell lines. TANGO expression was also examined in 171 cases of primary OSCC by immunohistochemistry and statistically assessed the correlation between TANGO positivity and the clinicopathological parameters including vessel density. By TANGO knockdown in OSCC cells, the growth and invasion were repressed and apoptosis was induced. Activities of platelet-derived growth factor beta polypeptide (PDGFB) and Neuropilin2 were inhibited by TANGO knockdown. TANGO immunoreactivity was detected in 35.1% (60/171) cases of OSCC. TANGO expression was strongly associated with tumour progression, nodal metastasis, clinical stage and number of blood or lymph vessels in OSCC. Patients showing TANGO-expression fared significantly worse disease-free survival than cases without TANGO expression. These findings suggest that TANGO might promote angiogenesis and lymphangiogenesis by upregulation of PDGFB and Neuropilin2 in OSCC. (C) 2014 Elsevier Ltd. All rights reserved.