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IKBKE通过Hippo信号通路调节人类恶性胶质瘤的细胞增殖和上皮-间质转化。

IKBKE regulates cell proliferation and epithelial-mesenchymal transition of human malignant glioma via the Hippo pathway.

作者信息

Lu Jie, Yang Yi, Guo Gaochao, Liu Yang, Zhang Zhimeng, Dong Shicai, Nan Yang, Zhao Zhenyi, Zhong Yue, Huang Qiang

机构信息

Department of Neurosurgery, Tianjin Medical University General Hospital, Heping District, Tianjin 300052, China.

Department of Neurosurgery, Tianjin Baodi People's Hospital, Baodi District, Tianjin 301800, China.

出版信息

Oncotarget. 2017 Jul 25;8(30):49502-49514. doi: 10.18632/oncotarget.17738.

Abstract

IKBKE is increased in several types of cancers and is associated with tumour malignancy. In this study, we confirmed that IKBKE promoted glioma proliferation, migration and invasion in vitro. Then, we further discovered that IKBKE increased Yes-associated protein 1 (YAP1) and TEA domain family member 2 (TEAD2), two important Hippo pathway downstream factors, to induce an epithelial-mesenchymal transition (EMT), thus contributing to tumour invasion and metastasis. We also testified that YAP1 and TEAD2 promoted epithelial-mesenchymal transition (EMT) in malignant glioma. Furthermore, we constructed nude mouse subcutaneous and intracranial models to verify that IKBKE could attenuate U87-MG tumourigenicity in vivo. Collectively, our results suggest that IKBKE plays a pivotal role in regulating cell proliferation, invasion and epithelial-mesenchymal transition of malignant glioma cells in vitro and in vivo by impacting on the Hippo pathway. Therefore, targeting IKBKE may become a new strategy to treat malignant glioma.

摘要

IKBKE在多种癌症中表达上调,并与肿瘤恶性程度相关。在本研究中,我们证实IKBKE在体外促进胶质瘤的增殖、迁移和侵袭。然后,我们进一步发现IKBKE增加了Yes相关蛋白1(YAP1)和TEA结构域家族成员2(TEAD2)这两个重要的Hippo通路下游因子,以诱导上皮-间质转化(EMT),从而促进肿瘤侵袭和转移。我们还证实YAP1和TEAD2促进恶性胶质瘤中的上皮-间质转化(EMT)。此外,我们构建了裸鼠皮下和颅内模型,以验证IKBKE在体内可减弱U87-MG的致瘤性。总体而言,我们的结果表明,IKBKE通过影响Hippo通路在体外和体内调节恶性胶质瘤细胞的增殖、侵袭和上皮-间质转化中起关键作用。因此,靶向IKBKE可能成为治疗恶性胶质瘤的新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01fe/5564784/69d9b9c58a6d/oncotarget-08-49502-g001.jpg

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