Astrocyte elevated gene-1(AEG-1) induces epithelial-mesenchymal transition in lung cancer through activating Wnt/β-catenin signaling.
Astrocyte elevated gene-1(AEG-1) induces epithelial-mesenchymal transition in lung cancer through activating Wnt/β-catenin signaling.
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星形胶质细胞升高基因 1 (AEG-1) 通过激活 Wnt/β-连环蛋白信号诱导肺癌上皮间质转化
DOI：
10.1186/s12885-015-1124-1
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发表时间：
2015-03-08
期刊：
影响因子：
3.8
通讯作者：
Ke Z
中科院分区：
文献类型：
--
作者：
He W;He S;Wang Z;Shen H;Fang W;Zhang Y;Qian W;Lin M;Yuan J;Wang J;Huang W;Wang L;Ke Z
背景：非小细胞肺癌（NSCLC）是一种高度转移的癌症，治疗选择有限，因此需要开发针对非小细胞肺癌的新疗法。在转移的早期阶段，癌细胞经历上皮-间质转化（EMT），这一阶段已知参与了Wnt/β-catenin信号传导。同时，AEG-1已被证明在一些恶性肿瘤中激活wnt介导的信号。方法：采用人非小细胞肺癌细胞系和裸鼠非小细胞肺癌异种移植细胞系研究AEG-1对EMT的影响。western blot、免疫荧光和免疫组织化学检测EMT或Wnt/β-catenin通路相关蛋白。结果：在本研究中，我们发现星形胶质细胞升高的基因-1（AEG-1）异位过表达促进了EMT，其原因是肺癌细胞系和临床肺癌标本中E-cadherin下调，Vimentin上调。通过原位异种移植小鼠模型，我们还观察到人类癌细胞中AEG-1的过表达导致了多个淋巴结转移的发展和间充质标志物（如Vimentin）的升高，这是EMT细胞的特征。此外，AEG-1通过直接靶向Wnt/β-catenin信号级联的多个阳性调节因子（包括GSK-3β和CKIδ），在EMT调控中发挥关键蛋白的作用。值得注意的是，转移性癌组织中AEG-1的过表达与NSCLC患者的低生存率密切相关。结论：这些结果揭示了AEG-1在EMT中的关键作用，并提示AEG-1可能是一种预后生物标志物，其靶向抑制可能被用作非小细胞肺癌的新治疗方法。
Background:Non-small cell lung cancer (NSCLC) is a highly metastatic cancer with limited therapeutic options, so development of novel therapies that target NSCLC is needed. During the early stage of metastasis, the cancer cells undergo an epithelial-mesenchymal transition (EMT), a phase in which Wnt/β-catenin signaling is known to be involved. Simultaneously, AEG-1 has been demonstrated to activate Wnt-mediated signaling in some malignant tumors.Methods:Human NSCLC cell lines and xenograft of NSCLC cells in nude mice were used to investigate the effects of AEG-1 on EMT. EMT or Wnt/β-catenin pathway-related proteins were characterized by western blot, immunofluorescence and immunohistochemistry.Results:In the present study, we demonstrated that astrocyte elevated gene-1(AEG-1) ectopic overexpression promoted EMT, which resulted from the down-regulation of E-cadherin and up-regulation of Vimentin in lung cancer cell lines and clinical lung cancer specimens. Using an orthotopic xenograft-mouse model, we also observed that AEG-1 overexpression in human carcinoma cells led to the development of multiple lymph node metastases and elevated mesenchymal markers such as Vimentin, which is a characteristic of cells in EMT. Furthermore, AEG-1 functioned as a critical protein in the regulation of EMT by directly targeting multiple positive regulators of the Wnt/β-catenin signaling cascade, including GSK-3β and CKIδ. Notably, overexpression of AEG-1 in metastatic cancer tissues was closely associated with poor survival of NSCLC patients.Conclusions:These results reveal the critical role of AEG-1 in EMT and suggest that AEG-1 may be a prognostic biomarker and its targeted inhibition may be utilized as a novel therapy for NSCLC.
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影响因子：
50.3
作者：
Hu G;Chong RA;Yang Q;Wei Y;Blanco MA;Li F;Reiss M;Au JL;Haffty BG;Kang Y
通讯作者：
Kang Y
DOI：
10.1038/jid.2008.445
发表时间：
2009-07
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
Chien AJ;Conrad WH;Moon RT
通讯作者：
Moon RT
星形胶质细胞升高基因 1 通过抑制转录因子 FOXO1 促进乳腺癌增殖
影响因子：
8
作者：
Li, J.;Yang, L.;Li, M.
通讯作者：
Li, M.
影响因子：
2.3
作者：
Liu, Kunmei;Guo, Le;Zhao, Wei
通讯作者：
Zhao, Wei
影响因子：
4
作者：
Hoppler, Stefan;Kavanagh, Claire Louise
通讯作者：
Kavanagh, Claire Louise