Microenvironment-derived regulation of HIF signaling drives transcriptional heterogeneity in glioblastoma multiforme
Heiland DH, Gaebelein A, Börries M, Wörner J, Pompe N, Franco P, Heynckes S, Bartholomae M, hAilín DÓ, Carro MS, Prinz M, Weber S, Mader I, Delev D, Schnell O.
Mol Cancer Res. online article
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. Implications: Transcriptional subclasses of glioblastoma multiforme are heterogeneously distributed within the same tumor. This study uncovered a regulatory function of the tumor microenvironment by metabolism-driven transcriptional reprogramming in infiltrating glioma cells.
