Activation of 5-lipoxygenase is required for nicotine mediated epithelial-mesenchymal transition and tumor cell growth
Publication in refereed journal


摘要Nicotine is shown to be one of the carcinogenic agents for gastric cancer Perturbation of epithelial-mesenchymal transition (EMT) results in loss of intracellular adhesions leading to tumor progression In this study, we examined the underlying mechanism of the long-term effects of nicotine on tumor progression in human gastric cancer cells Nicotine activated 5-lipoxygenase (5-LOX) in three gastric cancer cell lines (MKN-45, MKN-28 and AGS) Cells treated with nicotine dose- and time-dependently induced cell proliferation, invasion and suppressed apoptosis In addition, cell cycle progression analysis revealed that activation of 5-LOX modulated the G1/S phase transition regulatory proteins and caused cell proliferation MK886 (5-LOX activating protein inhibitor) mediated the induction of apoptosis by elevation of caspase-3 and Bax/Bc12 ratio. Abrogation of 5-LOX repressed featured molecular markers of EMT (inactivation of E-cadherin and activation of transcriptional repressor Snail). Blockade of 5-LOX signaling resulted in downregulation of cyclin D1, matrix metalloproteinase (MMP-7, -9), urokinase plasminogen activator (uPA) and its receptor (uPAR), and pro-apoptotic proteins Furthermore, suppression of Snail and induction of E-cadherin is extracellular signal-regulated kinase (Erk)-dependent. Thus, we conclude that the promotion effect of nicotine on cancer cell progression and EMT is mediated by Erk/5-LOX signaling pathway (C) 2009 Elsevier Ireland Ltd All rights reserved
著者Shin VY, Jin HC, Ng EKO, Sung JJY, Chu KM, Cho CH
期刊名稱Cancer Letters
詳細描述To ORKTS: doi: 10.1016/j.canlet.2009.12.011
頁次237 - 245
關鍵詞5-LOX; E-cadherin; EMT; Gastric cancer; Nicotine; Snail
Web of Science 學科類別Oncology; ONCOLOGY

上次更新時間 2020-20-11 於 23:44