一般注記type:Thesis
Malic enzyme 1 (ME1) is a multifunctional protein involved in glycolysis, the citric acid cycle, NADPH production, glutamine metabolism, and lipogenesis. It is overexpressed in various cancers. We examined the expression of ME1 in 119 oral squamous cell carcinomas (OSCCs) using immunohistochemistry. Malic enzyme 1 expression was moderate to strong in 57 (48%) OSCCs and correlated with pT, pN, clinical stage, and histological grade. In 37 cases with prognostic evaluation, moderate to strong ME1 expression indicated a worse prognosis than did weak ME1 expression. Malic enzyme 1 knockdown or inactivation by lanthanide inhibited cell proliferation and motility and suppressed the epithelial-mesenchymal transition in HSC3 human OSCC cells. Knockdown of ME1 also shifted energy metabolism from aerobic glycolysis and lactate fermentation to mitochondrial oxidative phosphorylation, and the redox status from reductive to oxidative. In a mouse tumor model, lanthanide suppressed tumor growth and increased survival time. These findings reveal that ME1 is a valid target for molecular therapy in OSCC.
博士(医学)・乙第1420号・平成30年9月26日
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License(https://creativecommons.org/licenses/by-nc/4.0/), which permits use, distribution and repro duction in any medium, provided the original work is properly cited and is not used for commercial purposes.
©2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
identifier:Cancer science Vol.109 No.6 p.2036-2045 (2018 Jun)
identifier:13479032
identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3498
identifier:Cancer science, 109(6): 2036-2045
連携機関・データベース国立情報学研究所 : 学術機関リポジトリデータベース(IRDB)(機関リポジトリ)
提供元機関・データベース奈良県立医科大学 : 奈良県立医科大学機関リポジトリ GINMU