title: TGF-β Regulates Survivin to Affect Cell Cycle and the Expression of EGFR and MMP9 in Glioblastoma.
abstract: Transforming growth factor beta (TGF-β) is suggestive of a molecular target for cancer therapy due to its involvement in cell cycle, differentiation, and morphogenesis. Meanwhile, survivin is identified as an apoptosis inhibitor and involved in tumorgenesis. Here, we aimed to investigate the potential associations between TGF-β and survivin in glioblastoma U87 cell line. Survivin small interfering RNA (siRNA), Western blotting, and cell cycle analysis were introduced to detect relevant proteins in TGF-β pathways. In this study, we observed a concentration- and time-dependent increase of survivin expression after treatment with TGF-β1. However, the kinase inhibitors U0126 and LY294002 inhibited the upregulation of survivin in comparison with DMSO. In addition, survivin siRNA effectively abrogated survivin expression in U87 cells, therefore affected cells' entry into the S phase of cell cycle, and then repressed the expression of epidermal growth factor receptor (EGFR) and matrix metalloproteinase 9 (MMP9) in comparison with non-transfection. In conclusion, the present study shows that TGF-β upregulates survivin expression via ERK and PI3K/AKT pathway, leading to glioblastoma cell cycle progression. Thus, the blockade of survivin will allow for the treatment of glioblastoma, partially attributing to the inhibition of EGFR and MMP9 expression.
authors: Department of Pharmacology, Guangzhou Medical University, Guangzhou, 510182, China.
authors: Wenliang
authors: W
authors: Chen
authors: Department of Paediatrics, the Affiliated Xiaolan People's Hospital of Southern Medical University, Guangdong, Zhongshan, 528415, China.
authors: Xiao
authors: X
authors: Zhong
authors: Department of Pharmacology, Guangzhou Medical University, Guangzhou, 510182, China.
authors: Yi
authors: Y
authors: Wei
authors: Department of Pharmacology, Guangzhou Medical University, Guangzhou, 510182, China.
authors: Yun
authors: Y
authors: Liu
authors: Department of Pharmacology, Guangzhou Medical University, Guangzhou, 510182, China.
authors: Quan
authors: Q
authors: Yi
authors: Department of Pharmacology, Guangzhou Medical University, Guangzhou, 510182, China.
authors: Genshui
authors: G
authors: Zhang
authors: Department of Pharmacology, Guangzhou Medical University, Guangzhou, 510182, China.
authors: Lishan
authors: L
authors: He
authors: Department of Pharmacology, Guangzhou Medical University, Guangzhou, 510182, China.
authors: Fajiang
authors: F
authors: Chen
authors: Department of Pharmacology, Guangzhou Medical University, Guangzhou, 510182, China.
authors: Yingping
authors: Y
authors: Liu
authors: Department of Pharmacology, Guangzhou Medical University, Guangzhou, 510182, China. luojiandong@gzhmu.edu.cn.|Guangzhou Institute of Cardiovascular Disease, Guangzhou Key Laboratory of Cardiovascular Disease, the Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China. luojiandong@gzhmu.edu.cn.
authors: Jiandong
authors: J
authors: Luo
mesh_terms: D001932:Brain Neoplasms / Q000201:enzymology / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005909:Glioblastoma / Q000201:enzymology* / Q000473:pathology*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000077022:Survivin; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; D016212:Transforming Growth Factor beta; D019869:Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D020780:Matrix Metalloproteinase 9
keywords: Cell cycle; EGFR; MMP9; Survivin; TGF-β