Into Thin Air: Hypoxia Drives Metabolic and Epigenomic Deregulation of Lethal Pediatric Ependymoma

Englinger, Bernhard; Hack, Olivia A.; Filbin, Mariella G.

doi:10.1016/j.devcel.2020.06.020

Cited by 1 publication

(1 citation statement)

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“…Hypoxia has recently been recognized as an oncogenic driver of PFA by reshaping its metabolic and epigenetic landscape [ 172 ]. Low oxygen concentration promotes optimal growth of PFA cells and induces glucose dependency and upregulation of glycolytic and hypoxia-related programs, that are prominent in PFA tumors with respect to normal brain and other EPN groups [ 23 , 151 ].…”

Section: Determinants Of Ithmentioning

confidence: 99%

Cell-of-Origin and Genetic, Epigenetic, and Microenvironmental Factors Contribute to the Intra-Tumoral Heterogeneity of Pediatric Intracranial Ependymoma

Servidei

Lucchetti

Navarra

et al. 2021

Cancers

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Intra-tumoral heterogeneity (ITH) is a complex multifaceted phenomenon that posits major challenges for the clinical management of cancer patients. Genetic, epigenetic, and microenvironmental factors are concurrent drivers of diversity among the distinct populations of cancer cells. ITH may also be installed by cancer stem cells (CSCs), that foster unidirectional hierarchy of cellular phenotypes or, alternatively, shift dynamically between distinct cellular states. Ependymoma (EPN), a molecularly heterogeneous group of tumors, shows a specific spatiotemporal distribution that suggests a link between ependymomagenesis and alterations of the biological processes involved in embryonic brain development. In children, EPN most often arises intra-cranially and is associated with an adverse outcome. Emerging evidence shows that EPN displays large intra-patient heterogeneity. In this review, after touching on EPN inter-tumoral heterogeneity, we focus on the sources of ITH in pediatric intra-cranial EPN in the framework of the CSC paradigm. We also examine how single-cell technology has shed new light on the complexity and developmental origins of EPN and the potential impact that this understanding may have on the therapeutic strategies against this deadly pediatric malignancy.

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Section: Determinants Of Ithmentioning

confidence: 99%