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

Blood Cancer Journal
J XiongW-L Zhao

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-α (Chokα). In T-lymphoma cells, pharmacological and molecular silencing of Chokα 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, Chokα 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, Chokα possessed oncogenic activity and could be a potential therapeutic target in TCL, as well as other hematological malignancies with interrupted Ras signaling pathways.

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Citations

Jul 26, 2016·Frontiers in Oncology·Marina BagnoliDelia Mezzanzanica
Jun 9, 2018·Pharmaceutical Patent Analyst·Hermann Am Mucke
Nov 9, 2019·Journal of Physics. Condensed Matter : an Institute of Physics Journal·Yuxia GaoZhaoming Tian
Dec 13, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Samantha GokhalePing Xie
Apr 7, 2020·Nature Reviews. Cancer·Danilo FioreGiorgio Inghirami
Jul 22, 2018·International Journal of Molecular Sciences·Andrea RizzoDelia Mezzanzanica
Feb 21, 2021·Cancer & Metabolism·Jesus Pacheco-TorresZaver M Bhujwalla
Jun 3, 2021·Pharmaceutics·Juan Carlos LacalJoaquín M Campos
Jun 25, 2021·Progress in Lipid Research·Yang ZhaoSylvain G Bourgoin
Jul 3, 2021·Pharmaceutics·Samantha Gokhale, Ping Xie
Aug 21, 2021·Bioorganic & Medicinal Chemistry Letters·Francesca QuartieriPaola Gnocchi

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Methods Mentioned

BETA
reverse transcription-PCR
PCR
flow cytometry
Pull-down
Assay
Co-Immunoprecipitation
ELISA
transmission
X-ray
transfection

Software Mentioned

Inveon Acquisition Workplace
Inveon Research Workplace ( IRW )
OSEM3D
MEV
FastMAP
SPSS
MarkerLynx Applications Manager
SIMCA
CalcuSyn

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