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

被引：42

作者：

Chang, Yingwei ^{[1
]}

Wu, Qianqian ^{[1
]}

Tian, Ting ^{[1
]}

Li, Li ^{[1
]}

Guo, Xuyan ^{[1
]}

Feng, Zhuoying ^{[1
]}

Zhou, Junchen ^{[1
]}

Zhang, Luping ^{[1
]}

Zhou, Shuai ^{[1
]}

Feng, Guoying ^{[1
]}

Han, Fengchan ^{[1
]}

Yang, Jun ^{[2
]}

Huang, Fei ^{[1
]}

机构：

[1] Binzhou Med Univ, Otol & Neurosci Ctr, Inst Human Anat & Histol & Embryol, Laishan Dist 264003, Shandong, Peoples R China

[2] Binzhou Med Univ, Yantai Affiliated Hosp, Neurosurg, Muping Area 264003, Shandong, Peoples R China

来源：

TUMOR BIOLOGY | 2015年 / 36卷 / 08期

基金：

中国博士后科学基金; 中国国家自然科学基金;

关键词：

SRPK1; Glioma; Akt; Metastasis; Apoptosis; Angiogenesis; INDUCIBLE FACTOR 1-ALPHA; SPLICING FACTORS; MESSENGER-RNA; GROWTH; PROTEIN; CANCER; EXPRESSION; KINASE; BAX; PHOSPHORYLATION;

D O I：

10.1007/s13277-015-3289-2

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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.

引用

页码：6083 / 6093

页数：11

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