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  • Chen, DongfengLund University,Lunds universitet,Neurokirurgi,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Rausinglaboratoriet i Lund - Tumörsektionen,Forskargrupper vid Lunds universitet,Neurosurgery,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Rausing laboratory of Lund - Tumor section,Lund University Research Groups (author)

Glioma Cell Proliferation Controlled by ERK Activity-Dependent Surface Expression of PDGFRA.

  • Article/chapterEnglish2014

Publisher, publication year, extent ...

  • 2014-01-29
  • Public Library of Science (PLoS),2014
  • electronicrdacarrier

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  • LIBRIS-ID:oai:lup.lub.lu.se:feaab906-36ca-40a8-b717-e576e8940d47
  • https://lup.lub.lu.se/record/4335822URI
  • https://doi.org/10.1371/journal.pone.0087281DOI

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  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

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  • Increased PDGFRA signaling is an essential pathogenic factor in many subtypes of gliomas. In this context the cell surface expression of PDGFRA is an important determinant of ligand sensing in the glioma microenvironment. However, the regulation of spatial distribution of PDGFRA in glioma cells remains poorly characterized. Here, we report that cell surface PDGFRA expression in gliomas is negatively regulated by an ERK-dependent mechanism, resulting in reduced proliferation of glioma cells. Glioma tumor tissues and their corresponding cell lines were isolated from 14 patients and analyzed by single-cell imaging and flow cytometry. In both cell lines and their corresponding tumor samples, glioma cell proliferation correlated with the extent of surface expression of PDGFRA. High levels of surface PDGFRA also correlated to high tubulin expression in glioma tumor tissue in vivo. In glioma cell lines, surface PDGFRA declined following treatment with inhibitors of tubulin, actin and dynamin. Screening of a panel of small molecule compounds identified the MEK inhibitor U0126 as a potent inhibitor of surface PDGFRA expression. Importantly, U0126 inhibited surface expression in a reversible, dose- and time-dependent manner, without affecting general PDGFRA expression. Treatment with U0126 resulted in reduced co-localization between PDGFRA and intracellular trafficking molecules e.g. clathrin, RAB11 and early endosomal antigen-1, in parallel with enhanced co-localization between PDGFRA and the Golgi cisternae maker, Giantin, suggesting a deviation of PDGFRA from the endosomal trafficking and recycling compartment, to the Golgi network. Furthermore, U0126 treatment in glioma cells induced an initial inhibition of ERK1/2 phosphorylation, followed by up-regulated ERK1/2 phosphorylation concomitant with diminished surface expression of PDGFRA. Finally, down-regulation of surface PDGFRA expression by U0126 is concordant with reduced glioma cell proliferation. These findings suggest that manipulation of spatial expression of PDGFRA can potentially be used to combat gliomas.

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  • Zuo, DuoBeijing Normal University (author)
  • Luan, ChengLund University,Lunds universitet,Diabetes - öpatofysiologi,Forskargrupper vid Lunds universitet,Diabetes - Islet Patophysiology,Lund University Research Groups(Swepub:lu)med-cgl (author)
  • Min, LiuLund University,Lunds universitet,Neurokirurgi,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Rausinglaboratoriet i Lund - Tumörsektionen,Forskargrupper vid Lunds universitet,Neurosurgery,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Rausing laboratory of Lund - Tumor section,Lund University Research Groups(Swepub:lu)med-lum (author)
  • Na, ManliLund University,Lunds universitet,Neurokirurgi,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Rausinglaboratoriet i Lund - Tumörsektionen,Forskargrupper vid Lunds universitet,Neurosurgery,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Rausing laboratory of Lund - Tumor section,Lund University Research Groups(Swepub:lu)med-min (author)
  • Ran, LiangBeijing Normal University (author)
  • Sun, YingyuBeijing Normal University (author)
  • Persson, AnnetteLund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)pat-ape (author)
  • Englund, ElisabetLund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)pat-een (author)
  • Salford, LeifLund University,Lunds universitet,Neurokirurgi,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Rausinglaboratoriet i Lund - Tumörsektionen,Forskargrupper vid Lunds universitet,Neurosurgery,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Rausing laboratory of Lund - Tumor section,Lund University Research Groups(Swepub:lu)nkir-lsa (author)
  • Renström, ErikLund University,Lunds universitet,Diabetes - öpatofysiologi,Forskargrupper vid Lunds universitet,Diabetes - Islet Patophysiology,Lund University Research Groups(Swepub:lu)mphy-ere (author)
  • Fan, XiaolongBeijing Normal University(Swepub:lu)molm-xfa (author)
  • Zhang, EnmingLund University,Lunds universitet,Diabetes - öpatofysiologi,Forskargrupper vid Lunds universitet,Diabetes - Islet Patophysiology,Lund University Research Groups(Swepub:lu)med-ezg (author)
  • NeurokirurgiSektion IV (creator_code:org_t)

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  • In:PLoS ONE: Public Library of Science (PLoS)9:11932-6203

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By the author/editor
Chen, Dongfeng
Zuo, Duo
Luan, Cheng
Min, Liu
Na, Manli
Ran, Liang
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Sun, Yingyu
Persson, Annette
Englund, Elisabe ...
Salford, Leif
Renström, Erik
Fan, Xiaolong
Zhang, Enming
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MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
and Basic Medicine
and Neurosciences
MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
and Clinical Medicin ...
and Cancer and Oncol ...
MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
and Clinical Medicin ...
and Neurology
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PLoS ONE
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Lund University

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