EGF-induced COX-2 enhances ANGPTL4 expression and promotes HNSCC metastasis

Abstract

Overexpression of EGFR is a common phenomenon in head and neck cancer squamous cancer cell (HNSCC) Activation of EGFR signaling pathway contributes to HNSCC metastasis and reduces patients’ survival In our previous studies we found that EGF-induced angiopoietin-like 4 (ANGPTL4) was involved in tumor metastasis However the mechanisms of EGF-induced ANGPTL4 and the functional roles of ANGPTL4 in HNSCC metastasis remain unclear In this study we found that EGF activated ERK but not NF-κB signaling pathway was involved in the regulation of ANGPTL4 expression In addition the expression of COX-2 was also induced in cells treated with EGF Furthermore we found that either inhibition of COX-2 activity using celecoxib or knockdown of COX-2 in cells inhibited EGF-induced ANGPTL4 expression PGE2 significantly induced the expression of ANGPTL4 mRNA and protein in time-dependent manners Inhibition of ERK activation dramatically blocked PGE2-induced ANGPTL4 mRNA expression In addition ANGPTL4 promoter containing with PPARE was enhanced by PGE2 In summary we found that EGF-induced ANGPTL4 expression via ERK and COX-2 signaling pathways Activation of ERK and the involvement of PPAR signaling may be essential for PGE2 enhanced ANGPTL4 expression The functional roles of ANGPTL4 regulated by COX-2 in HNSCC metastasis will be further studied

Date of Award	2015 Sept 10
Original language	English
Supervisor	Ben-Kuen Chen (Supervisor)