PTX3 gene activation in EGF-induced head and neck cancer cell metastasis.
PTX3 gene activation in EGF-induced head and neck cancer cell metastasis.
复制标题
EGF诱导的头颈癌细胞转移中的PTX3基因激活。
DOI：
10.18632/oncotarget.3482
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发表时间：
2015-04-10
期刊：
影响因子：
--
通讯作者：
Chen BK
中科院分区：
文献类型：
--
作者：
Chang WC;Wu SL;Huang WC;Hsu JY;Chan SH;Wang JM;Tsai JP;Chen BK
表皮生长因子（EGF）受体（EGFR）过表达与头颈部鳞状细胞癌（HNSCC）侵袭和转移增强相关。长五聚蛋白PTX 3参与癌细胞的免疫逃逸。在这里，我们确定PTX 3作为介导EGF诱导的HNSCC转移的促进因子。EGF诱导的PTX 3转录激活是通过c-Jun与PTX 3启动子的激活蛋白（AP）-1结合位点的结合。PI 3 K/Akt和NF-κB B是PTX 3激活的关键。EGF诱导的PTX 3表达在c-Jun和NF-κ B敲低的细胞中被阻断。EGF介导的PTX 3分泌导致细胞迁移和侵袭的增强，以及癌细胞和内皮细胞之间的相互作用。尾静脉注射动物模型揭示了PTX 3的消耗减少了肺的EGF引发的肿瘤细胞转移性接种。此外，纤维连接蛋白、基质金属蛋白酶9（MMP 9）和E-钙粘蛋白是EGFR/PTX 3介导的肿瘤转移的重要组成部分。总之，PI 3 K/Akt和NF-κ B依赖的AP-1调节介导了PTX 3对EGF的转录反应。EGF诱导的PTX 3的自分泌产生反过来诱导转移分子，激活炎症级联反应和转移。
Overexpression of the epidermal growth factor (EGF) receptor (EGFR) is associated with enhanced invasion and metastasis in head and neck squamous cell carcinoma (HNSCC). Long Pentraxin PTX3 is involved in immune escape in cancer cells. Here, we identified PTX3 as a promoting factor that mediates EGF-induced HNSCC metastasis. EGF-induced PTX3 transcriptional activation is via the binding of c-Jun to the activator protein (AP)-1 binding site of the PTX3 promoter. PI3K/Akt and NF-κB were essential for the PTX3 activation. EGF-induced PTX3 expression was blocked in c-Jun- and NF-κB-knockdown cells. EGF-mediated PTX3 secretion resulted in the enhancement of cell migration and invasion, and interactions between cancer and endothelial cells. The tail-vein injection animal model revealed that depletion of PTX3 decreased EGF-primed tumor cell metastatic seeding of the lungs. In addition, fibronectin, matrix metalloproteinase-9 (MMP9) and E-cadherin were essential components in EGFR/PTX3-mediated cancer metastasis. In conclusion, PI3K/Akt and NF-κB-dependent regulation of AP-1 mediates PTX3 transcriptional responses to EGF. Autocrine production of EGF-induced PTX3 in turn induces metastatic molecules, activating inflammatory cascades and metastasis.
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