TY  - JOUR
A1  - Ilina, Elena
A1  - Armento, Angela
A1  - Sanchez, Leticia
A1  - Reichlmeir, Marina
A1  - Braun, Yannick
A1  - Penski, Cornelia
A1  - Capper, David
A1  - Sahm, Felix
A1  - Jennewein, Lukas
A1  - Harter, Patrick Nikolaus
A1  - Zukunft, Sven
A1  - Fleming, Ingrid
A1  - Schulte, Dorothea
A1  - Guerroué, Francois
A1  - Behrends, Christian
A1  - Ronellenfitsch, Michael Wilfried
A1  - Naumann, Ulrike
A1  - Mittelbronn, Michel Guy André
T1  - Effects of soluble CPE on glioma cell migration are associated with mTOR activation and enhanced glucose flux
T2  - Oncotarget
N2  - 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.
KW  - CPE
KW  - glioblastoma
KW  - migration
KW  - metabolism
KW  - mTOR
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/44703
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-447033
SN  - 1949-2553
N1  - Licensed under a Creative Commons Attribution 3.0 License. http://creativecommons.org/licenses/by/3.0/
VL  - 8
IS  - 40
SP  - 67567
EP  - 67591
PB  - Impact Journals LLC
CY  - [S.l.]
ER  -