title: Transcriptional upregulation of microtubule-associated protein 2 is involved in the protein kinase A-induced decrease in the invasiveness of glioma cells.
abstract: BACKGROUND
  Malignant glioma is the most lethal primary tumor of the central nervous system, with notable cell invasion causing significant recurrence. Suppression of glioma invasion is very important for improving clinical outcomes. Drugs that directly disrupt the cytoskeleton have been developed for this purpose; however, drug resistance and unsatisfactory selectivity have limited their clinical use. Previously, we reported that protein kinase A (PKA, also known as cyclic-AMP dependent protein kinase) activation induced the differentiation of glioma cells.
  
  
  METHODS
  We used several small molecular inhibitors and RNA interference, combined with wound healing assays, Matrigel transwell assay, and microscopic observation, to determine whether activation of the PKA pathway could inhibit the invasion of human glioma cells.
  
  
  RESULTS
  Activation of PKA decreased the invasion of glioma cells. The mechanism operated via transcriptional upregulation of microtubule-associated protein 2 (MAP2), which was activated by the PKA pathway and led to ossification of microtubule dynamics via polymerization of tubulin. This resulted in morphological changes and a reduction in glioma cell invasion. Furthermore, chromosome immunoprecipitation and quantitative real-time polymerase chain reaction showed that signal transducer and activator of transcription 3 (STAT3) is involved in the transcriptional upregulation of MAP2.
  
  
  CONCLUSIONS
  Our findings suggested that PKA may represent a potential target for anti-invasion glioma therapy and that the downstream modulators (eg, STAT3/MAP2) partially mediate the effects of PKA.
authors.affiliation: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China (Y.Z., S.W., Y.L., K.L., B.L., M.S., Y.H., W.Z., D.X., J.H., G.Y.); Department of Neurosurgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China (C.L.); Department of Imaging, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China (Y.Z., Z.K.); Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China (J.H.).
authors.forename: Yuxi
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China (Y.Z., S.W., Y.L., K.L., B.L., M.S., Y.H., W.Z., D.X., J.H., G.Y.); Department of Neurosurgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China (C.L.); Department of Imaging, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China (Y.Z., Z.K.); Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China (J.H.).
authors.forename: Sihan
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China (Y.Z., S.W., Y.L., K.L., B.L., M.S., Y.H., W.Z., D.X., J.H., G.Y.); Department of Neurosurgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China (C.L.); Department of Imaging, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China (Y.Z., Z.K.); Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China (J.H.).
authors.forename: Chaofeng
authors.initials: C
authors.lastname: Liang
authors.affiliation: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China (Y.Z., S.W., Y.L., K.L., B.L., M.S., Y.H., W.Z., D.X., J.H., G.Y.); Department of Neurosurgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China (C.L.); Department of Imaging, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China (Y.Z., Z.K.); Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China (J.H.).
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China (Y.Z., S.W., Y.L., K.L., B.L., M.S., Y.H., W.Z., D.X., J.H., G.Y.); Department of Neurosurgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China (C.L.); Department of Imaging, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China (Y.Z., Z.K.); Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China (J.H.).
authors.forename: Yan
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China (Y.Z., S.W., Y.L., K.L., B.L., M.S., Y.H., W.Z., D.X., J.H., G.Y.); Department of Neurosurgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China (C.L.); Department of Imaging, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China (Y.Z., Z.K.); Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China (J.H.).
authors.forename: Kai
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China (Y.Z., S.W., Y.L., K.L., B.L., M.S., Y.H., W.Z., D.X., J.H., G.Y.); Department of Neurosurgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China (C.L.); Department of Imaging, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China (Y.Z., Z.K.); Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China (J.H.).
authors.forename: Bingzheng
authors.initials: B
authors.lastname: Lu
authors.affiliation: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China (Y.Z., S.W., Y.L., K.L., B.L., M.S., Y.H., W.Z., D.X., J.H., G.Y.); Department of Neurosurgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China (C.L.); Department of Imaging, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China (Y.Z., Z.K.); Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China (J.H.).
authors.forename: Minfeng
authors.initials: M
authors.lastname: Shu
authors.affiliation: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China (Y.Z., S.W., Y.L., K.L., B.L., M.S., Y.H., W.Z., D.X., J.H., G.Y.); Department of Neurosurgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China (C.L.); Department of Imaging, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China (Y.Z., Z.K.); Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China (J.H.).
authors.forename: Yijun
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China (Y.Z., S.W., Y.L., K.L., B.L., M.S., Y.H., W.Z., D.X., J.H., G.Y.); Department of Neurosurgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China (C.L.); Department of Imaging, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China (Y.Z., Z.K.); Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China (J.H.).
authors.forename: Wenbo
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China (Y.Z., S.W., Y.L., K.L., B.L., M.S., Y.H., W.Z., D.X., J.H., G.Y.); Department of Neurosurgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China (C.L.); Department of Imaging, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China (Y.Z., Z.K.); Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China (J.H.).
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Kang
authors.affiliation: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China (Y.Z., S.W., Y.L., K.L., B.L., M.S., Y.H., W.Z., D.X., J.H., G.Y.); Department of Neurosurgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China (C.L.); Department of Imaging, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China (Y.Z., Z.K.); Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China (J.H.).
authors.forename: Dong
authors.initials: D
authors.lastname: Xu
authors.affiliation: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China (Y.Z., S.W., Y.L., K.L., B.L., M.S., Y.H., W.Z., D.X., J.H., G.Y.); Department of Neurosurgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China (C.L.); Department of Imaging, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China (Y.Z., Z.K.); Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China (J.H.).
authors.forename: Jun
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China (Y.Z., S.W., Y.L., K.L., B.L., M.S., Y.H., W.Z., D.X., J.H., G.Y.); Department of Neurosurgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China (C.L.); Department of Imaging, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China (Y.Z., Z.K.); Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China (J.H.).
authors.forename: Guangmei
authors.initials: G
authors.lastname: Yan
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D005910:Glioma / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D051381:Rats; D015398:Signal Transduction; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: C489788:MAP2 protein, human; D008869:Microtubule-Associated Proteins; D017868:Cyclic AMP-Dependent Protein Kinases
keywords: MAP2; cAMP/PKA pathway; invasion; malignant glioma; microtubule