Epithelial mesenchymal transition induced by the CXCL9/CXCR3 axis through AKT activation promotes invasion and metastasis in tongue squamous cell carcinoma

Epithelial mesenchymal transition induced by the CXCL9/CXCR3 axis through AKT activation promotes invasion and metastasis in tongue squamous cell carcinoma
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CXCL9/CXCR3轴通过AKT激活诱导上皮间质转化促进舌鳞状细胞癌的侵袭和转移

DOI:
10.3892/or.2017.6169
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发表时间:
2018-03-01
期刊:
影响因子:
4.2
通讯作者:
He, Yongwen
He, Yongwen
中科院分区:
医学3区
文献类型:
--
作者:
Li, Ziliang;Liu, Jianqi;He, Yongwen

文献摘要

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本研究旨在探讨趋化因子CXCL 9/受体CXCR 3轴在舌鳞状细胞癌(TSCC)中诱导上皮-间质转化(EMT)、侵袭和转移的作用,揭示其内在机制,为口腔癌转移的预防和治疗提供新的思路。采用免疫组化法检测TSCC组织标本中CXCL 9和CXCR 3的表达水平,比较有无颈淋巴结转移的TSCC组织标本中CXCL 9和CXCR 3的表达差异。此外,TSCC Cal-27细胞系中的蛋白质表达或活性通过中和抗体、基因转染或敲除来控制。CCK-8法、细胞划痕法、Transwell法和细胞骨架染色法检测细胞增殖、迁移、侵袭和细胞骨架的变化。免疫荧光和Western blot检测Cal-27细胞EMT标志物(E-cadherin和vimentin)的变化。采用Western blotting检测Akt 2、p-Akt 2、eIF 4 E和p-eIF 4 E蛋白表达水平,探讨CXCL 9/CXCR 3轴在肿瘤侵袭转移中的调控作用及机制。CXCL 9和CXCR 3在有淋巴结转移的组织中的表达水平显著高于无淋巴结转移的组织(P
The present study aimed to assess the induction of epithelial-mesenchymal transition (EMT), invasion, and metastasis by the chemokine CXCL9/receptor CXCR3 axis in tongue squamous cell carcinoma (TSCC), unveiling the underlying mechanisms and providing new insights into the prevention and treatment of oral cancer metastasis. The expression levels of CXCL9 and CXCR3 in TSCC tissue specimens were determined by immunohistochemistry, assessing differences between samples with cervical lymph node metastasis and those without. Moreover, protein expression or activity in the TSCC Cal-27 cell line was controlled by neutralizing antibodies, gene transfection, or knock-out. Then, alterations of cell proliferation, migration, invasion, and the cytoskeleton were analyzed by CCK-8, cell scratch, Transwell, and cytoskeleton staining assays, respectively. Alterations of EMT markers (E-cadherin and vimentin) in Cal-27 cells were detected by immunofluorescence and western blotting. In addition, western blotting was utilized to detect protein expression levels of Akt2, p-Akt2, eIF4E and p-eIF4E, and to explore the regulatory roles and mechanisms of the CXCL9/CXCR3 axis in invasion and metastasis. Significantly increased expression levels of CXCL9 and CXCR3 were detected in tissue specimens with lymph node metastasis compared with those without (P