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High Podocalyxin levels promote cell viability partially through up-regulation of Annexin A2

Leefa, Isabelle LU ; Prost, Gaëlle LU ; Williams, Jennifer A.; Moss, Stephen E. and Nuber, Ulrike A. LU (2016) In Biochemical and Biophysical Research Communications 478(2). p.573-579
Abstract

Podocalyxin (PODXL) is a highly glycosylated and sialylated transmembrane protein that is up-regulated in various types of tumors and whose expression levels positively correlate with tumor grade. We previously found Podxl to be highly expressed in murine tumorigenic neural stem/progenitor cells (NSPs). Here we investigated the effects of elevated Podxl levels in these cells. NSPs overexpressing Podxl did not form brain tumors upon intracranial transplantations, indicating that high levels of this gene alone are not sufficient for tumor initiation. However, Podxl overexpression had a positive effect on cell number, sphere formation and cell viability, indicating that it might in this way contribute to the development and/or maintenance... (More)

Podocalyxin (PODXL) is a highly glycosylated and sialylated transmembrane protein that is up-regulated in various types of tumors and whose expression levels positively correlate with tumor grade. We previously found Podxl to be highly expressed in murine tumorigenic neural stem/progenitor cells (NSPs). Here we investigated the effects of elevated Podxl levels in these cells. NSPs overexpressing Podxl did not form brain tumors upon intracranial transplantations, indicating that high levels of this gene alone are not sufficient for tumor initiation. However, Podxl overexpression had a positive effect on cell number, sphere formation and cell viability, indicating that it might in this way contribute to the development and/or maintenance of tumors. Proteome analyses of Podxl-overexpressing and control NSPs revealed increased levels of Annexin A2 (ANXA2). We also found increased transcript levels, indicating that PODXL stimulates expression of the Anxa2 gene. Lack of Anxa2 in Podxl-overexpressing NSPs resulted in reduced viability of these cells, suggesting that PODXL-mediated pro-survival effects can at least in part be explained by increased ANXA2 levels. Finally, our data indicate that Podxl overexpression activates the MAP kinase (MAPK) pathway which in turn up-regulates Anxa2 expression. Our data indicate a novel molecular connection between PODXL and ANXA2: both exert pro-survival effects in NSPs, and PODXL positively regulates ANXA2 expression through the MAPK pathway.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Annexin A2, Cell viability, MAPK pathway, Neural stem/progenitor cells, Podocalyxin
in
Biochemical and Biophysical Research Communications
volume
478
issue
2
pages
7 pages
publisher
Elsevier
external identifiers
  • scopus:84995596064
  • wos:000383528600011
ISSN
0006-291X
DOI
10.1016/j.bbrc.2016.07.102
language
English
LU publication?
yes
id
064a74ab-274d-4c05-a8ed-6a682db41163
date added to LUP
2016-12-07 14:44:18
date last changed
2017-01-01 08:42:30
@article{064a74ab-274d-4c05-a8ed-6a682db41163,
  abstract     = {<p>Podocalyxin (PODXL) is a highly glycosylated and sialylated transmembrane protein that is up-regulated in various types of tumors and whose expression levels positively correlate with tumor grade. We previously found Podxl to be highly expressed in murine tumorigenic neural stem/progenitor cells (NSPs). Here we investigated the effects of elevated Podxl levels in these cells. NSPs overexpressing Podxl did not form brain tumors upon intracranial transplantations, indicating that high levels of this gene alone are not sufficient for tumor initiation. However, Podxl overexpression had a positive effect on cell number, sphere formation and cell viability, indicating that it might in this way contribute to the development and/or maintenance of tumors. Proteome analyses of Podxl-overexpressing and control NSPs revealed increased levels of Annexin A2 (ANXA2). We also found increased transcript levels, indicating that PODXL stimulates expression of the Anxa2 gene. Lack of Anxa2 in Podxl-overexpressing NSPs resulted in reduced viability of these cells, suggesting that PODXL-mediated pro-survival effects can at least in part be explained by increased ANXA2 levels. Finally, our data indicate that Podxl overexpression activates the MAP kinase (MAPK) pathway which in turn up-regulates Anxa2 expression. Our data indicate a novel molecular connection between PODXL and ANXA2: both exert pro-survival effects in NSPs, and PODXL positively regulates ANXA2 expression through the MAPK pathway.</p>},
  author       = {Leefa, Isabelle and Prost, Gaëlle and Williams, Jennifer A. and Moss, Stephen E. and Nuber, Ulrike A.},
  issn         = {0006-291X},
  keyword      = {Annexin A2,Cell viability,MAPK pathway,Neural stem/progenitor cells,Podocalyxin},
  language     = {eng},
  month        = {09},
  number       = {2},
  pages        = {573--579},
  publisher    = {Elsevier},
  series       = {Biochemical and Biophysical Research Communications},
  title        = {High Podocalyxin levels promote cell viability partially through up-regulation of Annexin A2},
  url          = {http://dx.doi.org/10.1016/j.bbrc.2016.07.102},
  volume       = {478},
  year         = {2016},
}