The influence of SRPK1 on glioma apoptosis, metastasis, and angiogenesis through the PI3K/Akt signaling pathway under normoxia
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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.
KeywordsSRPK1 Glioma Akt Metastasis Apoptosis Angiogenesis
This study was supported by the Key Project of National Natural Science Foundation of Shandong Province (ZR 2009CL004) and China Postdoctoral Science Foundation (20100481466). We also acknowledge the Pharmaceutical Health Science and Technology Development Program of Shandong Province (2011QZ001) and National Natural Science Foundation of China (81171142/H0910, 81271092) for funding this research, as well as a Project of Shandong Province Higher Educational Science and Technology Program (J11LF61).
Conflicts of interest
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