The influence of SRPK1 on glioma apoptosis, metastasis, and angiogenesis through the PI3K/Akt signaling pathway under normoxia

The influence of SRPK1 on glioma apoptosis, metastasis, and angiogenesis through the PI3K/Akt signaling pathway under normoxia
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常氧条件下SRPK1通过PI3K/Akt信号通路对胶质瘤细胞凋亡、转移和血管生成的影响

DOI:
10.1007/s13277-015-3289-2
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发表时间:
2015-08-01
期刊:
影响因子:
--
通讯作者:
Huang, Fei
Huang, Fei
中科院分区:
其他
文献类型:
--
作者:
Chang, Yingwei;Wu, Qianqian;Huang, Fei

文献摘要

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Gliomas, the most common primary brain tumors, have low survival rates and poorly defined molecular mechanisms to target for treatment. Serine/arginine SR protein kinases 1 (SRPK1) can highly and specifically phosphorylate the SR protein found in many tumors, which can influence cell proliferation and angiogenesis. However, the roles and regulatory mechanisms of SRPK1 in gliomas are not understood. The aim of this study was to determine the functions and regulation of SRPK1 in gliomas. We found that SRPK1 inhibition induces early apoptosis and significantly inhibits xenograft tumor growth. Our results indicate that SRPK1 affects Akt and eIF4E phosphorylation, Bax and Bcl-2 activation, and HIF-1 and VEGF production in glioma cells. Moreover, transfection of SRPK1 siRNA strongly reduced cell invasion and migration by regulating the expression of MMP2 and MMP9 and significantly decreased the volume of tumors and angiogenesis. We show here that a strong link exists among SRPK1, Akt, eIF4E, HIF-1, and VEGF activity that is functionally involved in apoptosis, metastasis, and angiogenesis of gliomas under normoxic conditions. Thus, SRPK1 may be a potential anticancer target to inhibit glioma progression.