Journal
MOLECULAR CANCER RESEARCH
Volume 16, Issue 4, Pages 655-668Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1541-7786.MCR-17-0680
Keywords
-
Categories
Funding
- German Cancer Society (Seeding Grand TII)
- Muller-Fahnenberg Stiftung
- German Federal Ministry of Education and Research (BMBF) [FKZ 01ZX1409B]
- Deutsche Forschungsgemeinschaft Germany
Ask authors/readers for more resources
The evolving and highly heterogeneous nature of malignant brain tumors underlies their limited response to therapy and poor prognosis. In addition to genetic alterations, highly dynamic processes, such as transcriptional and metabolic reprogramming, play an important role in the development of tumor heterogeneity. The current study reports an adaptive mechanism in which the metabolic environment of malignant glioma drives transcriptional reprogramming. Multiregional analysis of a glioblastoma patient biopsy revealed a metabolic landscape marked by varying stages of hypoxia and creatine enrichment. Creatine treatment and metabolism was further shown to promote a synergistic effect through upregulation of the glycine cleavage system and chemical regulation of prolyl-hydroxylase domain. Consequently, creatine maintained a reduction of reactive oxygen species and change of the alpha-ketoglutarate/succinate ratio, leading to an inhibition of HIF signaling in primary tumor cell lines. These effects shifted the transcriptional pattern toward a proneural subtype and reduced the rate of cell migration and invasion in vitro. (c) 2018 AACR.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available