Effects of soluble CPE on glioma cell migration are associated with mTOR activation and enhanced glucose flux

Carboxypeptidase E (CPE) has recently been described as a multifunctional protein that regulates proliferation, migration and survival in several tumor entities. In glioblastoma (GBM), the most malignant primary brain tu
Carboxypeptidase E (CPE) has recently been described as a multifunctional protein that regulates proliferation, migration and survival in several tumor entities. In glioblastoma (GBM), the most malignant primary brain tumor, secreted CPE (sCPE) was shown to modulate tumor cell migration. In our current study, we aimed at clarifying the underlying molecular mechanisms regulating anti-migratory as well as novel metabolic effects of sCPE in GBM. Here we show that sCPE activates mTORC1 signaling in glioma cells detectable by phosphorylation of its downstream target RPS6. Additionally, sCPE diminishes glioma cell migration associated with a negative regulation of Rac1 signaling via RPS6, since both inhibition of mTOR and stimulation of Rac1 results in a reversed effect of sCPE on migration. Knockdown of CPE leads to a decrease of active RPS6 associated with increased GBM cell motility. Apart from this, we show that sCPE enhances glucose flux into the tricarboxylic acid cycle at the expense of lactate production, thereby decreasing aerobic glycolysis, which might as well contribute to a less invasive behavior of tumor cells. Our data contributes to a better understanding of the complexity of GBM cell migration and sheds new light on how tumor cell invasion and metabolic plasticity are interconnected.
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Metadaten
Author:Elena Ilina, Angela Armento, Leticia Sanchez, Marina Reichlmeir, Yannick Braun, Cornelia Penski, David Capper, Felix Sahm, Lukas Jennewein, Patrick Nikolaus Harter, Sven Zukunft, Ingrid Fleming, Dorothea Schulte, Francois Guerroué, Christian Behrends, Michael Wilfried Ronellenfitsch, Ulrike Naumann, Michel Guy André Mittelbronn
URN:urn:nbn:de:hebis:30:3-447033
DOI:http://dx.doi.org/10.18632/oncotarget.18747
ISSN:1949-2553
Parent Title (English):Oncotarget
Publisher:Impact Journals LLC
Place of publication:[S.l.]
Document Type:Article
Language:English
Year of Completion:2017
Date of first Publication:2017/06/27
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2017/10/26
Tag:CPE; glioblastoma; mTOR; metabolism; migration
Volume:8
Issue:40
Pagenumber:25
First Page:67567
Last Page:67591
Note:
Licensed under a Creative Commons Attribution 3.0 License. http://creativecommons.org/licenses/by/3.0/
HeBIS PPN:450643794
Institutes:Medizin
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 3.0

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