表皮生長因子在促進癌症轉移的過程中扮演了決定性的角色。而癌細胞貼附在血管內皮細胞上在癌症轉移中為重要的第一步。此外，纖維連接蛋白被認為在促進癌症外滲過程中癌細胞與內皮細胞之間的黏附為重要的角色。我們初步的數據表明表皮生長因子誘導的纖維連接蛋白在頭頸癌細胞中是透過五端非翻譯區來穩定纖維連接蛋白mRNA的穩定性。然而，表皮生長因子所誘導的纖維連接蛋白表現量的確切機制仍然是未知的。值得注意的是，我們也證實核仁素以及異質核核醣核蛋白A2 / B1透過穩定纖維連接蛋白mRNA來增加其表現量。在這項研究中，我們觀察到抑制核仁素以及異質核核醣核蛋白A2 / B1會降低表皮生長因子所誘導的纖維連接蛋白表現量。這些結果表明核仁素以及異質核核醣核蛋白A2 / B1可能在表皮生長因子介導的纖連蛋白機制中扮演重要的角色。另外，我們同時也發現表皮生長因子會增強頭頸癌細胞和內皮細胞之間的黏附作用。本篇研究在探討表皮生長因子所誘發纖維連接蛋白表現量對於頭頸癌細胞與內皮細胞交互作用的相關機制。在此實驗中，我們在模擬血液循環系統中利用壓制FaDu細胞中的核仁素表現會抑制表皮生長因子所誘導的纖維連接蛋白表現量，進而導致FaDu細胞與內皮細胞之間黏附作用降低。由於癌細胞與內皮細胞之間的黏附作用非常重要，因此我們想知道在癌細胞黏附於內皮細胞上後，內皮細胞的通透性是否會改變。更進一步的，我們發現在處理過表皮生長因子後由FaDu細胞所分泌的纖維連接蛋白會改變內皮細胞的通透性。並且在抑制FaDu細胞中的纖連蛋白降低了內皮細胞的通透性。綜合上述，我們可知FaDu細胞中的纖維連接蛋白扮演重要的因子，會去增強癌細胞與內皮細胞之間的黏附作用，以便於促進腫瘤的轉移。

Epidermal growth factor (EGF) has been highlighted as an important role to promote metastasis in human cancer. Moreover, fibronectin serving as an attachment point for extravasation and affecting the progression of cell migration. Our preliminary data indicated that EGF-enhanced fibronectin up-regulation in head and neck squamous cell carcinoma (HNSCC) was through stabilizing mRNA by fibronectin 5’ untranslated region (5’-UTR). However, the precise mechanism of EGF-enhanced fibronectin expression still remains elusive. Notably, our unpublished data demonstrated that nucleolin (NCL) and hnRNP A2/B1 (A2B1) can stabilized fibronectin mRNA. In this study, we observed that knockdown of NCL and A2B1 inhibited EGF-induced fibronectin expression. These results suggested that NCL and A2B1 might be crucial in the mechanisms of EGF-mediated fibronectin upregulation. The attachment of cancer cells to endothelial cells is required during the initial steps of metastatic. To further figure out how EGF-enhanced HNSCC metastasis, we used dynamic flow circulation to mimic blood circulatory system. We found that EGF increased the interaction between HNSCC and endothelial cells. Therefore, we also confirmed silencing NCL and fibronectin in FaDu cells resulted in reducing the interaction between FaDu cells and endothelial cells. Besides, we wanted to elucidate whether the permeability of endothelial cells will change after tumor cells attaching to the endothelial cells. Then, by using transwell permeability assay we found that EGF induced the permeability of endothelial cells. Moreover, EGF-enhanced the secreted fibronectin in FaDu cells and leaded to the increase of permeability in endothelial cells, while knocking down fibronectin in FaDu cells decreased the endothelial cells permeability. Taken together, results of this study indicated that fibronectin in FaDu cells act as an important activator to mediate the activation of FaDu and endothelial cells interactions and the permeability of endothelial cells.

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