Evidence map›Paper›PMID 25468898›Full record

ArticleNeuro-oncology2015

Protein kinase A-dependent phosphorylation of Dock180 at serine residue 1250 is important for glioma growth and invasion stimulated by platelet derived-growth factor receptor α.

Haizhong Feng, Yanxin Li, Yuhua Yin, Weiwei Zhang, Yanli Hou, Lei Zhang, Zuoqing Li, Baoshu Xie, Wei-Qiang Gao, Jann N Sarkaria and 5 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuro-oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
0.9field-weighted citation impact, top 29% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 33 citations in OpenAlex.

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  11. Targeting Rac and Cdc42 GEFs in Metastatic Cancer.Frontiers in cell and developmental biology · 2020
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  16. Review
  17. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 7 institutions in 2 countries.

Haizhong FengState Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (H.F., W.Z., Y.H., L.Z., Z.L., W.-Q.G., S.-Y.C.); Department of Neurology, Northwestern Brain Tumor Institute, Center for Genetic Medicine, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (H.F., J.J.R., B.H., S.-Y.C.); Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.L.); Department of Neurological Surgery (Y.Y., B.X.); Department of Radiotherapy, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.H.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Department of Neurological Surgery, Northwestern Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (C.D.J., A.T.P.).
Yanxin LiState Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (H.F., W.Z., Y.H., L.Z., Z.L., W.-Q.G., S.-Y.C.); Department of Neurology, Northwestern Brain Tumor Institute, Center for Genetic Medicine, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (H.F., J.J.R., B.H., S.-Y.C.); Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.L.); Department of Neurological Surgery (Y.Y., B.X.); Department of Radiotherapy, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.H.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Department of Neurological Surgery, Northwestern Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (C.D.J., A.T.P.).
Yuhua YinState Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (H.F., W.Z., Y.H., L.Z., Z.L., W.-Q.G., S.-Y.C.); Department of Neurology, Northwestern Brain Tumor Institute, Center for Genetic Medicine, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (H.F., J.J.R., B.H., S.-Y.C.); Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.L.); Department of Neurological Surgery (Y.Y., B.X.); Department of Radiotherapy, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.H.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Department of Neurological Surgery, Northwestern Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (C.D.J., A.T.P.).
Weiwei ZhangState Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (H.F., W.Z., Y.H., L.Z., Z.L., W.-Q.G., S.-Y.C.); Department of Neurology, Northwestern Brain Tumor Institute, Center for Genetic Medicine, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (H.F., J.J.R., B.H., S.-Y.C.); Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.L.); Department of Neurological Surgery (Y.Y., B.X.); Department of Radiotherapy, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.H.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Department of Neurological Surgery, Northwestern Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (C.D.J., A.T.P.).
Yanli HouState Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (H.F., W.Z., Y.H., L.Z., Z.L., W.-Q.G., S.-Y.C.); Department of Neurology, Northwestern Brain Tumor Institute, Center for Genetic Medicine, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (H.F., J.J.R., B.H., S.-Y.C.); Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.L.); Department of Neurological Surgery (Y.Y., B.X.); Department of Radiotherapy, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.H.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Department of Neurological Surgery, Northwestern Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (C.D.J., A.T.P.).
Lei ZhangState Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (H.F., W.Z., Y.H., L.Z., Z.L., W.-Q.G., S.-Y.C.); Department of Neurology, Northwestern Brain Tumor Institute, Center for Genetic Medicine, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (H.F., J.J.R., B.H., S.-Y.C.); Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.L.); Department of Neurological Surgery (Y.Y., B.X.); Department of Radiotherapy, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.H.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Department of Neurological Surgery, Northwestern Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (C.D.J., A.T.P.).
Zuoqing LiState Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (H.F., W.Z., Y.H., L.Z., Z.L., W.-Q.G., S.-Y.C.); Department of Neurology, Northwestern Brain Tumor Institute, Center for Genetic Medicine, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (H.F., J.J.R., B.H., S.-Y.C.); Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.L.); Department of Neurological Surgery (Y.Y., B.X.); Department of Radiotherapy, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.H.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Department of Neurological Surgery, Northwestern Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (C.D.J., A.T.P.).
Baoshu XieState Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (H.F., W.Z., Y.H., L.Z., Z.L., W.-Q.G., S.-Y.C.); Department of Neurology, Northwestern Brain Tumor Institute, Center for Genetic Medicine, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (H.F., J.J.R., B.H., S.-Y.C.); Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.L.); Department of Neurological Surgery (Y.Y., B.X.); Department of Radiotherapy, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.H.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Department of Neurological Surgery, Northwestern Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (C.D.J., A.T.P.).
Wei-Qiang GaoState Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (H.F., W.Z., Y.H., L.Z., Z.L., W.-Q.G., S.-Y.C.); Department of Neurology, Northwestern Brain Tumor Institute, Center for Genetic Medicine, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (H.F., J.J.R., B.H., S.-Y.C.); Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.L.); Department of Neurological Surgery (Y.Y., B.X.); Department of Radiotherapy, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.H.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Department of Neurological Surgery, Northwestern Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (C.D.J., A.T.P.).
Jann N SarkariaState Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (H.F., W.Z., Y.H., L.Z., Z.L., W.-Q.G., S.-Y.C.); Department of Neurology, Northwestern Brain Tumor Institute, Center for Genetic Medicine, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (H.F., J.J.R., B.H., S.-Y.C.); Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.L.); Department of Neurological Surgery (Y.Y., B.X.); Department of Radiotherapy, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.H.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Department of Neurological Surgery, Northwestern Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (C.D.J., A.T.P.).
Jeffery J RaizerState Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (H.F., W.Z., Y.H., L.Z., Z.L., W.-Q.G., S.-Y.C.); Department of Neurology, Northwestern Brain Tumor Institute, Center for Genetic Medicine, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (H.F., J.J.R., B.H., S.-Y.C.); Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.L.); Department of Neurological Surgery (Y.Y., B.X.); Department of Radiotherapy, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.H.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Department of Neurological Surgery, Northwestern Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (C.D.J., A.T.P.).
C David JamesState Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (H.F., W.Z., Y.H., L.Z., Z.L., W.-Q.G., S.-Y.C.); Department of Neurology, Northwestern Brain Tumor Institute, Center for Genetic Medicine, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (H.F., J.J.R., B.H., S.-Y.C.); Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.L.); Department of Neurological Surgery (Y.Y., B.X.); Department of Radiotherapy, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.H.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Department of Neurological Surgery, Northwestern Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (C.D.J., A.T.P.).
Andrew T ParsaState Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (H.F., W.Z., Y.H., L.Z., Z.L., W.-Q.G., S.-Y.C.); Department of Neurology, Northwestern Brain Tumor Institute, Center for Genetic Medicine, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (H.F., J.J.R., B.H., S.-Y.C.); Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.L.); Department of Neurological Surgery (Y.Y., B.X.); Department of Radiotherapy, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.H.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Department of Neurological Surgery, Northwestern Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (C.D.J., A.T.P.).
Bo HuState Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (H.F., W.Z., Y.H., L.Z., Z.L., W.-Q.G., S.-Y.C.); Department of Neurology, Northwestern Brain Tumor Institute, Center for Genetic Medicine, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (H.F., J.J.R., B.H., S.-Y.C.); Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.L.); Department of Neurological Surgery (Y.Y., B.X.); Department of Radiotherapy, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.H.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Department of Neurological Surgery, Northwestern Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (C.D.J., A.T.P.).
Shi-Yuan ChengState Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (H.F., W.Z., Y.H., L.Z., Z.L., W.-Q.G., S.-Y.C.); Department of Neurology, Northwestern Brain Tumor Institute, Center for Genetic Medicine, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (H.F., J.J.R., B.H., S.-Y.C.); Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.L.); Department of Neurological Surgery (Y.Y., B.X.); Department of Radiotherapy, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.H.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Department of Neurological Surgery, Northwestern Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (C.D.J., A.T.P.).
Shanghai Jiao Tong University · CNShanghai Children's Medical Center · CNMayo Clinic · USNorthwestern University · USState Key Laboratory of Oncogene and Related Genes · CNNeurological Surgery · USRobert H. Lurie Comprehensive Cancer Center of Northwestern University

Funding

Tumor Environment and Metastasis (TEAM) Research ProgramP30CA060553 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Daniela E Matei · 1993 to 2026
$153.9M
Targeted MV-CEA as a Potent Antitumor Agent against GBMP50CA108961 · NCI · MAYO CLINIC ROCHESTER · PI O'NEILL, BRIAN PATRICK · 2004 to 2015
$22.5M
BRAF Mutation in Malignant Astrocytoma Origin, Evolution, and Response to TherapyR01NS080619 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JAMES, CHARLES DAVID, PETRITSCH, CLAUDIA KATHARINA · 2012 to 2016
$1.8M
Modulation of Oncogenic Signaling in GlioblastomasR01CA159811 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI CHENG, SHI-YUAN · 2012 to 2016
$1.8M
Cdk4/6 Inhibitor Therapy for Glioblastoma MultiformeR01CA159467 · NCI · GEORGETOWN UNIVERSITY · PI JAMES, CHARLES DAVID, WALDMAN, TODD A · 2012 to 2016
$1.6M
NCI NIH HHS CA108961NCI NIH HHS CA159467NCI NIH HHS P30 CA060553NCI NIH HHS P50 CA108961NCI NIH HHS R01 CA159811NINDS NIH HHS NS080619
6 · The paper itself

Abstract

backgroundDedicator of cytokinesis 1 (Dock1 or Dock180), a bipartite guanine nucleotide exchange factor for Rac1, plays critical roles in receptor tyrosine kinase-stimulated cancer growth and invasion. Dock180 activity is required in cell migration cancer tumorigenesis promoted by platelet derived growth factor receptor (PDGFR) and epidermal growth factor receptor.

methodsTo demonstrate whether PDGFRα promotes tumor malignant behavior through protein kinase A (PKA)-dependent serine phosphorylation of Dock180, we performed cell proliferation, viability, migration, immunoprecipitation, immunoblotting, colony formation, and in vivo tumorigenesis assays using established and short-term explant cultures of glioblastoma cell lines.

resultsStimulation of PDGFRα results in phosphorylation of Dock180 at serine residue 1250 (S1250), whereas PKA inhibitors H-89 and KT5720 oppose this phosphorylation. S1250 locates within the Rac1-binding Dock homology region 2 domain of Dock180, and its phosphorylation activates Rac1, p-Akt, and phosphorylated extracellular signal-regulated kinase 1/2, while promoting cell migration, in vitro. By expressing RNA interference (RNAi)-resistant wild-type Dock180, but not mutant Dock180 S1250L, we were able to rescue PDGFRα-associated signaling and biological activities in cultured glioblastoma multiforme (GBM) cells that had been treated with RNAi for suppression of endogenous Dock180. In addition, expression of the same RNAi-resistant Dock180 rescued an invasive phenotype of GBM cells following intracranial engraftment in immunocompromised mice.

conclusionThese data describe an important mechanism by which PDGFRα promotes glioma malignant phenotypes through PKA-dependent serine phosphorylation of Dock180, and the data thereby support targeting the PDGFRα-PKA-Dock180-Rac1 axis for treating GBM with molecular profiles indicating PDGFRα signaling dependency.

Indexed as

AnimalsBrain NeoplasmsCarbazolesCell Line, TumorCell MovementCell ProliferationCell SurvivalCyclic AMP-Dependent Protein KinasesFemaleGlioblastomaHEK293 CellsHumansIsoquinolinesMicePhosphorylationPlatelet-Derived Growth FactorCarbazolesCyclic AMP-Dependent Protein KinasesDOCK1 protein, humanIsoquinolinesKT 5720N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamidePlatelet-Derived Growth Factorplatelet-derived growth factor AProtein Kinase InhibitorsPyrrolesrac GTP-Binding ProteinsReceptor, Platelet-Derived Growth Factor alphaSulfonamidesDock180glioblastomasPDGFRαphosphorylationPKA

Identifiers

PMID25468898
PMCPMC4483118
OpenAlexW2034598341

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