Hypoxia-induced PLOD2 promotes proliferation, migration and invasion via PI3K/Akt signaling in glioma.
Hypoxia-induced PLOD2 promotes proliferation, migration and invasion via PI3K/Akt signaling in glioma.
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缺氧诱导的 PLOD2 通过 PI3K/Akt 信号传导促进神经胶质瘤的增殖、迁移和侵袭。
DOI：
10.18632/oncotarget.16710
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发表时间：
2017-06-27
期刊：
影响因子：
--
通讯作者：
Qi S
中科院分区：
文献类型：
--
作者：
Song Y;Zheng S;Wang J;Long H;Fang L;Wang G;Li Z;Que T;Liu Y;Li Y;Zhang X;Fang W;Qi S
胶质瘤是最常见的恶性原发性脑肿瘤，5年生存率低。胶质瘤中存在PLOD 2的异常表达，但PLOD 2在胶质瘤中的具体作用及分子机制尚未见报道。在这项研究中，PLOD 2被发现在胶质瘤中频繁上调，可以作为一个独立的预后标志物来识别临床结果较差的患者。PLOD 2基因的敲除可抑制胶质瘤细胞的增殖、迁移和侵袭。PLOD 2的抑制可使PI 3 K/AKT信号通路失活，从而调节其下游上皮间质转化（EMT）相关调节因子的表达，包括E-cadherin、vimentin、N-cadherin、β-catenin、snail和slug。此外，缺氧诱导因子-1 α（HIF-1α）可通过缺氧诱导PLOD 2表达，从而促进缺氧诱导的胶质瘤细胞EMT。我们的数据表明PLOD 2可能是胶质瘤患者的潜在治疗靶点。
Gliomas are the most common form of malignant primary brain tumors with poor 5-year survival rate. Dysregulation of procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) was observed in gliomas, but the specific role and molecular mechanism of PLOD2 in glioma have not been reported yet. In this study, PLOD2 was found to be frequently up-regulated in glioma and could serve as an independent prognostic marker to identify patients with poor clinical outcome. Knockdown of PLOD2 inhibited proliferation, migration and invasion of glioma cells in vitro and in vivo. Mechanistically, inhibition of PLOD2 inactivated PI3K/AKT signaling pathway and thus regulated the expression of its downstream epithelial–mesenchymal transition (EMT)-associated regulators, including E-cadherin, vimentin, N-cadherin, β-catenin, snail and slug in glioma cells. Moreover, PLOD2 could be induced by hypoxia-inducible factor-1α (HIF-1α) via hypoxia, thereby promoting hypoxia-induced EMT in glioma cells. Our data suggests that PLOD2 may be a potential therapeutic target for patients with glioma.
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影响因子：
3.8
作者：
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EMT，癌症干细胞和耐药性：癌症战争中新兴的邪恶轴。
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影响因子：
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