title: The influence of SRPK1 on glioma apoptosis, metastasis, and angiogenesis through the PI3K/Akt signaling pathway under normoxia.
abstract: 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.
authors.affiliation: Institute of Human Anatomy and Histology and Embryology, Otology & Neuroscience Center, Binzhou Medical University, 346 Guanhai Road, Laishan District, Shandong Province, 264003, China.
authors.forename: Yingwei
authors.initials: Y
authors.lastname: Chang
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Wu
authors.forename: Ting
authors.initials: T
authors.lastname: Tian
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Xuyan
authors.initials: X
authors.lastname: Guo
authors.forename: Zhuoying
authors.initials: Z
authors.lastname: Feng
authors.forename: Junchen
authors.initials: J
authors.lastname: Zhou
authors.forename: Luping
authors.initials: L
authors.lastname: Zhang
authors.forename: Shuai
authors.initials: S
authors.lastname: Zhou
authors.forename: Guoying
authors.initials: G
authors.lastname: Feng
authors.forename: Fengchan
authors.initials: F
authors.lastname: Han
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Fei
authors.initials: F
authors.lastname: Huang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D051379:Mice; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009389:Neovascularization, Pathologic / Q000235:genetics; D051058:Oncogene Protein v-akt / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction; D023041:Xenograft Model Antitumor Assays
chemical_list: D009363:Neoplasm Proteins; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; C087728:SRPK1 protein, human
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