Glioma Cell Proliferation Controlled by ERK Activity-Dependent Surface Expression of PDGFRA.
Chen, Dongfeng LU ; Zuo, Duo ; Luan, Cheng LU ; Min, Liu LU ; Na, Manli LU ; Ran, Liang ; Sun, Yingyu ; Persson, Annette LU ; Englund, Elisabet LU
and Salford, Leif
LU
, et al.
(2014)
In PLoS ONE
9(1).
- Abstract
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4335822
- author
- Chen, Dongfeng
LU
; Zuo, Duo
; Luan, Cheng
LU
; Min, Liu
LU
; Na, Manli
LU
; Ran, Liang
; Sun, Yingyu
; Persson, Annette
LU
; Englund, Elisabet
LU
and Salford, Leif
LU
, et al. (More)
- Chen, Dongfeng
LU
; Zuo, Duo
; Luan, Cheng
LU
; Min, Liu
LU
; Na, Manli
LU
; Ran, Liang
; Sun, Yingyu
; Persson, Annette
LU
; Englund, Elisabet
LU
; Salford, Leif
LU
; Renström, Erik
LU
; Fan, Xiaolong
LU
and Zhang, Enming
LU
(Less)
- organization
- publishing date
- 2014
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS ONE
- volume
- 9
- issue
- 1
- article number
- e87281
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- pmid:24489888
- wos:000330570000129
- scopus:84900312351
- pmid:24489888
- ISSN
- 1932-6203
- DOI
- 10.1371/journal.pone.0087281
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Endocrinology (013241500), Pathology, (Lund) (013030000), Neurosurgery (013026000), Neural Plasticity and Repair (013210080), Islet patophysiology (013212132)
- id
- feaab906-36ca-40a8-b717-e576e8940d47 (old id 4335822)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/24489888?dopt=Abstract
- date added to LUP
- 2016-04-01 14:35:30
- date last changed
- 2022-03-22 00:51:12
@article{feaab906-36ca-40a8-b717-e576e8940d47,
abstract = {{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.}},
author = {{Chen, Dongfeng and Zuo, Duo and Luan, Cheng and Min, Liu and Na, Manli and Ran, Liang and Sun, Yingyu and Persson, Annette and Englund, Elisabet and Salford, Leif and Renström, Erik and Fan, Xiaolong and Zhang, Enming}},
issn = {{1932-6203}},
language = {{eng}},
number = {{1}},
publisher = {{Public Library of Science (PLoS)}},
series = {{PLoS ONE}},
title = {{Glioma Cell Proliferation Controlled by ERK Activity-Dependent Surface Expression of PDGFRA.}},
url = {{https://lup.lub.lu.se/search/files/4058450/4779729.pdf}},
doi = {{10.1371/journal.pone.0087281}},
volume = {{9}},
year = {{2014}},
}