Xia Tian, Tong Song, Fan Kai, Zhai Wei, Fang Bin, Wang Si-Hua, Wang Jian-Jun
Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, China.
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, China.
Am J Cancer Res. 2016 Sep 1;6(9):2031-2040. eCollection 2016.
X-box binding protein 1 (XBP1) was found to be overexpressed in glioma and breast cancers, suggesting that XBP1 might act as a potent oncogenic protein. However, the clinical significance and biological role of XBP1 in esophageal squamous cell carcinoma (ESCC) remain unknown. In this study, we report that XBP1 is markedly overexpressed in ESCC cell lines and clinical samples. XBP1 overexpression was significantly correlated with ESCC tumor stage, lymph node metastasis and poor outcome. A functional study demonstrated that XBP1 promoted cell growth and cell invasion both in and in . Further study found that the XBP1-mediated invasion and proliferation of cancer cells requires the up-regulation of matrix metalloproteinase-9 (MMP-9). Importantly, a significant correlation between XBP1 and MMP-9 levels was observed in ESCC clinical samples. Our findings demonstrate that XBP1 is an oncogene that plays an important role in the development of ESCC by activating MMP-9 expression.
X盒结合蛋白1(XBP1)在胶质瘤和乳腺癌中被发现过表达,这表明XBP1可能作为一种有效的致癌蛋白发挥作用。然而,XBP1在食管鳞状细胞癌(ESCC)中的临床意义和生物学作用仍不清楚。在本研究中,我们报道XBP1在ESCC细胞系和临床样本中显著过表达。XBP1过表达与ESCC肿瘤分期、淋巴结转移及不良预后显著相关。一项功能研究表明,XBP1在体内和体外均促进细胞生长和细胞侵袭。进一步研究发现,XBP1介导的癌细胞侵袭和增殖需要基质金属蛋白酶-9(MMP-9)的上调。重要的是,在ESCC临床样本中观察到XBP1与MMP-9水平之间存在显著相关性。我们的研究结果表明,XBP1是一种致癌基因,通过激活MMP-9表达在ESCC的发生发展中起重要作用。