Storkhead box 2 and melanoma inhibitory activity promote oral squamous cell carcinoma progression.

Storkhead box 2 and melanoma inhibitory activity promote oral squamous cell carcinoma progression.
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DOI:
10.18632/oncotarget.8495
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发表时间:
2016-05-03
期刊:
影响因子:
--
通讯作者:
Kuniyasu H
Kuniyasu H
中科院分区:
其他
文献类型:
--
作者:
Sasahira T;Nishiguchi Y;Fujiwara R;Kurihara M;Kirita T;Bosserhoff AK;Kuniyasu H

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斯托克黑德盒蛋白2(STOX2)是一种与子痫前期胎儿生长受限相关的转录因子。我们最近报道黑色素瘤抑制活性(MIA)促进口腔鳞状细胞癌(OSCC)的进展。然而,在恶性肿瘤中,STOX2和MIA之间的关系仍不清楚。应用免疫组织化学和聚合酶链式反应技术检测MIA和STOX2在口腔鳞癌中的表达。我们还对人口腔鳞状细胞癌细胞进行了功能分析。口腔鳞状细胞癌组织中MIA和STOX2基因表达水平均高于正常口腔黏膜上皮细胞,且STOX2基因表达上调与MIA基因过度表达显著相关。STOX2表达与淋巴结转移(P=0.0002)和MIA表达(P<0.0001)相关。此外,口腔鳞癌中MIA表达(P=0.0035)和STOX2表达(P=0.0061)与预后不良相关。体外口腔鳞状细胞癌细胞分析显示,MIA通过旁分泌方式增加STOX2的表达。此外,STOX2促进口腔鳞癌细胞生长、侵袭,抑制细胞凋亡,增强对紫杉醇、顺铂和5-FU的耐药性。我们的研究结果表明,MIA-STOX2信号通路可能是口腔鳞状细胞癌有用的诊断和治疗靶点。
Storkhead box protein 2 (STOX2) is a transcriptional factor associated with pre-eclampsia with fetal growth restriction. We recently reported that melanoma inhibitory activity (MIA) promotes oral squamous cell carcinoma (OSCC) progression. However, the relationship between STOX2 and MIA remains unknown in malignancies. We used immunohistochemistry and PCR to investigate MIA and STOX2 expression in OSCC. We also performed functional analysis in human OSCC cells. MIA and STOX2 mRNA levels were higher in OSCCs than in normal oral epithelial cells, and upregulation of STOX2 was significantly correlated with overexpression of MIA. Immunostaining for STOX2 was associated with nodal metastasis (P = 0.0002) and MIA expression (P < 0.0001). Furthermore, MIA expression (P = 0.0035) and STOX2 expression (P = 0.0061) were associated with poor outcome in OSCCs. In vitro analysis using OSCC cells revealed that MIA increased expression of STOX2 by paracrine manner. Moreover, STOX2 accelerated OSCC cell growth, invasion, suppressed apoptosis, and enhanced resistance to paclitaxel, cisplatin, and 5-FU. Our results suggest that MIA-STOX2 signaling may be a useful diagnostic and therapeutic target in OSCCs.
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