Expression of cytosolic malic enzyme (ME1) is associated with disease progression in human oral squamous cell carcinoma.
Expression of cytosolic malic enzyme (ME1) is associated with disease progression in human oral squamous cell carcinoma.
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DOI：
10.1111/cas.13594
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发表时间：
2018-06
期刊：
影响因子：
5.7
通讯作者：
Kuniyasu H
中科院分区：
文献类型：
--
作者：
Nakashima C;Yamamoto K;Fujiwara-Tani R;Luo Y;Matsushima S;Fujii K;Ohmori H;Sasahira T;Sasaki T;Kitadai Y;Kirita T;Kuniyasu H
苹果酸酶1(ME1)是一种多功能蛋白质，参与糖酵解、柠檬酸循环、NADPH的产生、谷氨酰胺代谢和脂肪生成。它在各种癌症中过度表达。应用免疫组织化学方法检测了119例口腔鳞状细胞癌(OSCC)中ME1的表达。苹果酸酶1在57例口腔鳞状细胞癌中呈中到强表达，且与PT、PN、临床分期和组织学分级有关。在37例有预后评估的病例中，ME1中强表达提示预后比弱ME1表达差。在HSC3人口腔鳞状细胞癌中，苹果酸酶1基因敲除或被稀土元素灭活可抑制细胞的增殖和运动，并抑制上皮细胞向间充质细胞的转化。ME1基因的敲除也使能量代谢从有氧糖酵解和乳酸发酵转移到线粒体氧化磷酸化，氧化还原状态从还原状态转变为氧化状态。在小鼠肿瘤模型中，稀土元素抑制了肿瘤生长，延长了生存时间。这些发现表明ME1是口腔鳞癌分子治疗的有效靶点。
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.
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影响因子：
8
作者：
Knoblich, Konstantin;Wang, Hong-Xing;Hemler, Martin E.
通讯作者：
Hemler, Martin E.
影响因子：
5.2
作者：
Grabacka MM;Wilk A;Antonczyk A;Banks P;Walczyk-Tytko E;Dean M;Pierzchalska M;Reiss K
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影响因子：
4.3
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Pacherník J
影响因子：
6
作者：
Kuniyasu, H;Yano, S;Ohmori, H
通讯作者：
Ohmori, H
影响因子：
1.9
作者：
POVEY, S;WILSON, DE;BUCKTON, KE
通讯作者：
BUCKTON, KE