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Dysregulated choline metabolism in T-cell lymphoma: role of choline kinase-? and therapeutic targeting.


ABSTRACT: Cancer cells have distinct metabolomic profile. Metabolic enzymes regulate key oncogenic signaling pathways and have an essential role on tumor progression. Here, serum metabolomic analysis was performed in 45 patients with T-cell lymphoma (TCL) and 50 healthy volunteers. The results showed that dysregulation of choline metabolism occurred in TCL and was related to tumor cell overexpression of choline kinase-? (Chok?). In T-lymphoma cells, pharmacological and molecular silencing of Chok? significantly decreased Ras-GTP activity, AKT and ERK phosphorylation and MYC oncoprotein expression, leading to restoration of choline metabolites and induction of tumor cell apoptosis/necropotosis. In a T-lymphoma xenograft murine model, Chok? inhibitor CK37 remarkably retarded tumor growth, suppressed Ras-AKT/ERK signaling, increased lysophosphatidylcholine levels and induced in situ cell apoptosis/necropotosis. Collectively, as a regulatory gene of aberrant choline metabolism, Chok? possessed oncogenic activity and could be a potential therapeutic target in TCL, as well as other hematological malignancies with interrupted Ras signaling pathways.

SUBMITTER: Xiong J 

PROVIDER: S-EPMC4382653 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Dysregulated choline metabolism in T-cell lymphoma: role of choline kinase-α and therapeutic targeting.

Xiong J J   Bian J J   Wang L L   Zhou J-Y JY   Wang Y Y   Zhao Y Y   Wu L-L LL   Hu J-J JJ   Li B B   Chen S-J SJ   Yan C C   Zhao W-L WL  

Blood cancer journal 20150313


Cancer cells have distinct metabolomic profile. Metabolic enzymes regulate key oncogenic signaling pathways and have an essential role on tumor progression. Here, serum metabolomic analysis was performed in 45 patients with T-cell lymphoma (TCL) and 50 healthy volunteers. The results showed that dysregulation of choline metabolism occurred in TCL and was related to tumor cell overexpression of choline kinase-α (Chokα). In T-lymphoma cells, pharmacological and molecular silencing of Chokα signifi  ...[more]

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