Epidermal growth factor-induced COX-2 regulates metastasis of head and neck squamous cell carcinoma through upregulation of angiopoietin-like 4

Kuo Hwa Chiang, Jiunn Min Shieh, Chih Jie Shen, Ting Wei Chang, Pei Ting Wu, Jinn Yuan Hsu, Jhih Peng Tsai, Wen Chang Chang, Ben Kuen Chen

研究成果: 雜誌貢獻文章同行評審

4 引文 斯高帕斯(Scopus)

摘要

Epidermal growth factor receptor (EGFR) expression and activation are the major causes of metastasis in cancers such as head and neck squamous cell carcinoma (HNSCC). However, the reciprocal effect of EGF-induced COX-2 and angiopoietin-like 4 (ANGPTL4) on HNSCC metastasis remains unclear. In this study, we revealed that the expression of ANGPTL4 is essential for COX-2-derived prostaglandin E2 (PGE2)-induced tumor cell metastasis. We showed that EGF-induced ANGPTL4 expression was dramatically inhibited with the depletion and inactivation of COX-2 by knockdown of COX-2 and celecoxib treatment, respectively. Prostaglandin E2 induced ANGPTL4 expression in a time- and dose-dependent manners in various HNSCC cell lines through the ERK pathway. In addition, the depletion of ANGPTL4 and MMP1 significantly impeded the PGE2-induced transendothelial invasion ability of HNSCC cells and the binding of tumor cells to endothelial cells. The induction of molecules involved in the regulation of epithelial-mesenchymal transition was also dependent on ANGPTL4 expression in PGE2-treated cells. The depletion of ANGPTL4 further blocked PGE2-primed tumor cell metastatic seeding of lungs. These results indicate that the EGF-activated PGE2/ANGPTL4 axis enhanced HNSCC metastasis. The concurrent expression of COX-2 and ANGPTL4 in HNSCC tumor specimens provides insight into potential therapeutic targets for the treatment of EGFR-associated HNSCC metastasis.
原文英語
頁(從 - 到)2004-2015
頁數12
期刊Cancer Science
111
發行號6
DOIs
出版狀態已發佈 - 六月 1 2020

ASJC Scopus subject areas

  • 腫瘤科
  • 癌症研究

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