Universität zu Köln

Schulze, M., Fedorchenko, O., Zink, T. G., Knobbe-Thomsen, C. B., Kraus, S., Schwinn, S., Beilhack, A., Reifenberger, G., Monoranu, C. M., Siren, A-L, Jeanclos, E. and Gohla, A. (2016). Chronophin is a glial tumor modifier involved in the regulation of glioblastoma growth and invasiveness. Oncogene, 35 (24). S. 3163 - 3178. LONDON: NATURE PUBLISHING GROUP. ISSN 1476-5594

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Abstract

Glioblastoma is the most aggressive primary brain tumor in adults. Although the rapid recurrence of glioblastomas after treatment is a major clinical challenge, the relationships between tumor growth and intracerebral spread remain poorly understood. We have identified the cofilin phosphatase chronophin (gene name: pyridoxal phosphatase, PDXP) as a glial tumor modifier. Monoallelic PDXP loss was frequent in four independent human astrocytic tumor cohorts and increased with tumor grade. We found that aberrant PDXP promoter methylation can be a mechanism leading to further chronophin downregulation in glioblastomas, which correlated with shorter glioblastoma patient survival. Moreover, we observed an inverse association between chronophin protein expression and cofilin phosphorylation levels in glioma tissue samples. Chronophin-deficient glioblastoma cells showed elevated cofilin phosphorylation, an increase in polymerized actin, a higher directionality of cell migration, and elevated in vitro invasiveness. Tumor growth of chronophin-depleted glioblastoma cells xenografted into the immunodeficient mouse brain was strongly impaired. Our study suggests a mechanism whereby the genetic and epigenetic alterations of PDXP resulting in altered chronophin expression may regulate the interplay between glioma cell proliferation and invasion.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Schulze, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Fedorchenko, O. UNSPECIFIED UNSPECIFIED UNSPECIFIED Zink, T. G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Knobbe-Thomsen, C. B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kraus, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schwinn, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Beilhack, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Reifenberger, G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Monoranu, C. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Siren, A-L UNSPECIFIED UNSPECIFIED UNSPECIFIED Jeanclos, E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gohla, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-272181
DOI:	10.1038/onc.2015.376
Journal or Publication Title:	Oncogene
Volume:	35
Number:	24
Page Range:	S. 3163 - 3178
Date:	2016
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	1476-5594
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MALIGNANT GLIOMA; CELL-LINE; COFILIN; INVASION; BRAIN; ADF/COFILIN; INHIBITION; LANDSCAPE; DELETION; MOTILITY Multiple languages Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/27218