Glucose deprivation promotes de-differentiation in lung adenocarcinoma

ABSTRACT: Increased utilization of glucose is a hallmark of cancer. Several studies are investigating the efficacy of glucose restriction on solid cancers, by glucose transporter blocking or glycolysis inhibition. However, the adaptations of cancer cells to glucose restriction are not known. Here, we report the discovery that glucose restriction in lung adenocarcinoma (LUAD) cells induces de-differentiation, leading to a more aggressive phenotype. Glucose deprivation causes a reduction in alpha-ketoglutarate (aKG), leading to attenuated activity of aKG-dependent histone demethylases and consequent histone hypermethylation. We further show that this de-differentiated and aggressive phenotype depends on unbalanced EZH2 activity, causing inhibition of prolyl-hydroxylase PHD3 and increased expression of

INSTRUMENT(S): NextSeq 500

ORGANISM(S): Homo sapiens

SUBMITTER: Giorgio Giurato 

PROVIDER: E-MTAB-11678 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress