| Literature DB >> 33479702 |
Angela Maria Savino1,2,3, Sara Isabel Fernandes4, Orianne Olivares5, Anna Zemlyansky6, Antony Cousins5, Elke K Markert5,7, Shani Barel1,2, Ifat Geron1,2, Liron Frishman1,2, Yehudit Birger2,6, Cornelia Eckert8, Sergey Tumanov7, Gillian MacKay7, Jurre J Kamphorst7,9, Pawel Herzyk10,11, Jonatan Fernández-García4, Ifat Abramovich4, Inbal Mor4, Michela Bardini12, Ersilia Barin3, Sudha Janaki-Raman13, Justin R Cross13, Michael G Kharas3, Eyal Gottlieb14, Shai Izraeli15,16,17,18, Christina Halsey19.
Abstract
Metabolic reprogramming is a key hallmark of cancer, but less is known about metabolic plasticity of the same tumor at different sites. Here, we investigated the metabolic adaptation of leukemia in two different microenvironments, the bone marrow and the central nervous system (CNS). We identified a metabolic signature of fatty-acid synthesis in CNS leukemia, highlighting Stearoyl-CoA desaturase (SCD1) as a key player. In vivo SCD1 overexpression increases CNS disease, whilst genetic or pharmacological inhibition of SCD1 decreases CNS load. Overall, we demonstrated that leukemic cells dynamically rewire metabolic pathways to suit local conditions and that targeting these adaptations can be exploited therapeutically.Entities:
Keywords: SCD1; acute lymphoblastic leukemia; central nervous system; fatty acid synthesis; metabolic reprogramming
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Year: 2020 PMID： 33479702 PMCID： PMC7116605 DOI： 10.1038/s43018-020-00115-2
Source DB: PubMed Journal: Nat Cancer ISSN： 2662-1347