Tu Ming, Wange Wei, Cai Lin, Zhu Penglei, Gao Zhichao, Zheng Weiming
Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Department of Emergency, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Tumour Biol. 2016 Nov;37(11):14701-14709. doi: 10.1007/s13277-016-5346-x. Epub 2016 Sep 14.
Glioma is a malignant tumor that affects all kinds of people all over the world. It demonstrates remarkable infiltrative and invasive features. The high expression of interleukin-13 receptor subunit alpha-2 (IL-13Rα2) reportedly plays a pivotal role in some cancers. However, whether IL-13Rα2 contributes to glioma remains unknown. This study demonstrates that IL-13Rα2 is significantly up-regulated in human glioma tissue samples. It is also associated with late stages of disease progression and diminished survival in glioma patients. Gain- and loss-of-function studies demonstrate that IL-13Rα2 promotes the growth, migration, and invasion of glioma cells. In addition, mechanistic investigations show that IL-13Rα2 activates Scr, phosphatidylinositol 3 kinase (PI3K), Akt, and mTOR. Also, restraining Scr in glioma cells attenuates the activation of Scr/PI3K/Akt/mTOR pathway by IL-13Rα2, whereas the silencing of Scr markedly rescues the pro-invasive effect of IL-13Rα2. In conclusion, our results suggest that the high expression of IL-13Rα2 is significantly associated with the growth and metastasis of human glioma cells via the Scr/PI3K/Akt/mTOR pathway, while IL-13Rα2 may be a potential therapeutic target for glioma treatment.
神经胶质瘤是一种影响全球各类人群的恶性肿瘤。它具有显著的浸润性和侵袭性特征。据报道,白细胞介素-13受体α2亚基(IL-13Rα2)的高表达在某些癌症中起关键作用。然而,IL-13Rα2是否与神经胶质瘤有关尚不清楚。本研究表明,IL-13Rα2在人类神经胶质瘤组织样本中显著上调。它还与疾病进展的晚期阶段以及神经胶质瘤患者生存率降低有关。功能获得和缺失研究表明,IL-13Rα2促进神经胶质瘤细胞的生长、迁移和侵袭。此外,机制研究表明,IL-13Rα2激活Scr、磷脂酰肌醇3激酶(PI3K)、Akt和mTOR。而且,抑制神经胶质瘤细胞中的Scr可减弱IL-13Rα2对Scr/PI3K/Akt/mTOR通路的激活,而沉默Scr则显著挽救IL-13Rα2的促侵袭作用。总之,我们的结果表明,IL-13Rα2的高表达通过Scr/PI3K/Akt/mTOR通路与人神经胶质瘤细胞的生长和转移显著相关,而IL-13Rα2可能是神经胶质瘤治疗的潜在靶点。