The 2nd International Conference on Applied Biochemistry and Biotechnology (ABB 2019)
July 21st-24th, 2019, Macau, China
Plenary Speakers
Prof. Hua-Wen Fu, Institute of Molecular and Cellular Biology & Department of Life Science, National Tsing Hua University

Dr. Hua-Wen Fu is an Associate Professor of Institute of Molecular and Cellular Biology & Department of Life Science at National Tsing Hua University (NTHU) in Taiwan, China. Her research focuses in the fields of molecular cell biology and protein chemistry with interests on the area of transmembrane signaling mediated through G protein-coupled receptors (GPCRs). She has been investigating the endocytosis and signaling of protease-activated receptor 1 (PAR1) and the role of PAR2 in cancer. Currently, she is also working on the characterization and identification of the receptors of Helicobactor pylori neutrophil-activating protein. Dr. Fu received her Ph.D. degree in Biochemistry from Duke University in 1998, completed her postdoctoral training at the Cardiovascular Research Institute of the University of California, San Francisco (UCSF), and has been the faculty member of NTHU in Hsinchu, Taiwan since 2000.

Speech Title: Protease-activated receptor 2 induces migration and promotes Slug-mediated epithelial-mesenchymal transition in lung adenocarcinoma cells

Abstract: Protease-activated receptor 2 (PAR2), a G protein-coupled receptors (GPCRs), is activated by trypsin-like serine proteases. The activation of PAR2 occurs by a proteolytic cleavage at a specific site by serine proteases to unmask the new N-terminus, which then act as a tethered ligand that binds intramolecularly to trigger the receptor activation. PAR2 not only mediates a variety of physiological responses but also participates in cancer progression. It has been reported that PAR2 contributes to cell growth, anti-apoptosis, and migration in lung cancer. Given that PAR2 activation in airway epithelial cells compromises the airway epithelium barrier by disruption of E-cadherin adhesion, PAR2 may be involved in epithelial-mesenchymal transition (EMT) in lung adenocarcinoma cells. In this study, we found that PAR2 is highly expressed in several lung adenocarcinoma cell lines. In two lung adenocarcinoma cell lines, CL1-5 and H1299 cells, activation of PAR2 induces migration and Slug-mediated EMT. The underlying mechanisms involved in PAR2-induced migration and EMT in CL1-5 cells were further investigated. We showed that PAR2-induced migration of CL1-5 cells is mediated by the Src/p38 mitogen-activated protein kinase (p38 MAPK) signalling pathway. β-arrestin 1, not G protein, is involved in this PAR2-mediated Src/p38 MAPK signalling pathway. PAR2-induced EMT in CL1-5 cells is dependent on the activation of extracellular-signal-regulated kinase 2 (ERK2). The activation of ERK2 further mediates Slug stabilization through suppressing the activity of glycogen synthase kinase 3β. Thus, PAR2 induces migration through β-arrestin 1-dependent activation of p38 MAPK and EMT through ERK2-mediated stabilization of Slug in lung adenocarcinoma cells. Our finding suggests that PAR2 might serve as a therapeutic target for metastatic lung cancer.

Keywords: PAR2, EMT, ERK1/2, β-arrestin, Slug, lung adenocarcinoma

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