title: High Podocalyxin levels promote cell viability partially through up-regulation of Annexin A2.
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 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.
authors.affiliation: Lund Strategic Center for Stem Cell Biology, Lund University, Lund, Sweden.
authors.forename: Isabelle V Leefa Chong
authors.initials: IV
authors.lastname: San
authors.affiliation: Lund Strategic Center for Stem Cell Biology, Lund University, Lund, Sweden.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Prost
authors.affiliation: Department of Cell Biology, University College London Institute of Ophthalmology, London, United Kingdom.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Williams
authors.affiliation: Department of Cell Biology, University College London Institute of Ophthalmology, London, United Kingdom.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Moss
authors.affiliation: Lund Strategic Center for Stem Cell Biology, Lund University, Lund, Sweden. Electronic address: nuber@bio.tu-darmstadt.de.
authors.forename: Ulrike A
authors.initials: UA
authors.lastname: Nuber
mesh_terms: D000818:Animals; D017306:Annexin A2 / Q000235:genetics* / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D015536:Down-Regulation; D020935:MAP Kinase Signaling System; D008810:Mice, Inbred C57BL; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D012795:Sialoglycoproteins / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: D017306:Annexin A2; D012795:Sialoglycoproteins; C001643:podocalyxin
keywords: Annexin A2; Cell viability; MAPK pathway; Neural stem/progenitor cells; Podocalyxin