EGFRvIII mediates hepatocellular carcinoma cell invasion by promoting S100 calcium binding protein A11 expression.
EGFRvIII mediates hepatocellular carcinoma cell invasion by promoting S100 calcium binding protein A11 expression.
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DOI：
10.1371/journal.pone.0083332
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Li Z
中科院分区：
文献类型：
--
作者：
Luo X;Xie H;Long X;Zhou M;Xu Z;Shi B;Jiang H;Li Z
表皮生长因子受体（EGFR）在癌症中经常异常表达，该受体下游的异常信号传导有助于肿瘤生长。EGFR变体III（EGFRvIII）是EGFR最常见的改变形式，含有截短的配体结合结构域。该受体下游的异常信号传导有助于肿瘤侵袭。我们先前报道了EGFRvIII可以促进肝细胞癌（HCC）的侵袭。然而，关于EGFRvIII介导的HCC细胞运动性和侵袭性增加的机制知之甚少。在这项研究中，我们观察到S100 A11在过表达EGFRvIII的Huh-7细胞中显著上调。此外，S100 A11表达在HCC组织样本中升高（68.6%; 35/51），并且这种升高与EGFRvIII表达相关（p = 0.0020; n = 20）。 此外，S100 A11的过表达可以促进HCC细胞的侵袭性，而针对S100 A11的siRNA可以抑制稳定转染EGFRvIII的HCC细胞的侵袭性。此外，STAT 3抑制剂可以阻断具有稳定的EGFRvIII过表达的HCC细胞中S100 A11表达和S100 A11启动子活性。此外，STATx结合位点的突变可以消除EGFRvIII对S1000 A11启动子活性的刺激。综上所述，结果表明EGFRvIII-STAT 3途径通过上调S100 A11促进细胞迁移和侵袭。
Epidermal growth factor receptor (EGFR) is frequently aberrantly expressed in cancer, and abnormal signalling downstream of this receptor contributes to tumour growth. EGFR variant III (EGFRvIII) is the most commonly altered form of EGFR and contains a truncated ligand-binding domain. Aberrant signalling downstream of this receptor contributes to tumour invasion. We previously reported that EGFRvIII can promote hepatocellular carcinoma (HCC) invasion. However, little is known concerning the mechanisms underlying EGFRvIII-mediated increases in cell motility and invasion in HCC. In this study, we observed that S100A11 was significantly upregulated in Huh-7 cells that overexpressed EGFRvIII. Moreover, S100A11 expression was elevated in HCC tissue samples (68.6%; 35/51), and this elevation was correlated with EGFRvIII expression (p = 0.0020; n = 20). Furthermore, the overexpression of S100A11 can promote HCC cell invasiveness, whereas siRNA against S100A11 can suppress the invasiveness of HCC cells stably transfected with EGFRvIII. Additionally, STAT3 inhibitors can block S100A11 expression and S100A11 promoter activity in HCC cells with stable overexpression of EGFRvIII. Furthermore, mutation in STATx binding sites could abolish the S1000A11 promoter activity stimulation by EGFRvIII. Taken together, the results demonstrate that the EGFRvIII-STAT3 pathway promotes cell migration and invasion by upregulating S100A11.
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影响因子：
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作者：
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DOI：
10.1016/s0360-3016(03)00511-x
发表时间：
2003-09-01
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通讯作者：
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