ArticlePloS one2009
Differential role of human choline kinase alpha and beta enzymes in lipid metabolism: implications in cancer onset and treatment.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 101 citations in OpenAlex.
- Biosynthesis of Phosphatidylethanolamine and Phosphatidylcholine via the Kennedy Pathway in Cancer and Other Pathological Conditions.International journal of molecular sciences · 2026Review
- Expression and prognostic value of cholesterol homeostasis genes in hepatocellular carcinoma: A cohort study based on TCGA.Medicine · 2026Article
- Article
- Cellular and organismal function of choline metabolism.Nature metabolism · 2025Review
- Choline supplementation mitigates effects of bilirubin in cerebellar granule neurons in vitro.Pediatric research · 2024Article
- Influence of pancreaticoduodenectomy for periampullary carcinoma on intestinal microbiome and metabolites.Heliyon · 2024Article
- Correlation between choline kinase alpha expression andScientific reports · 2023Article
- Differences in the metabolomic profile of the human palatine tonsil between pediatrics and adults.PloS one · 2023Article
- Review
- Anticancer Activity of the Choline Kinase Inhibitor PL48 Is Due to Selective Disruption of Choline Metabolism and Transport Systems in Cancer Cell Lines.Pharmaceutics · 2022Article
- The Metabolic Signature of AML Cells Treated With Homoharringtonine.Frontiers in oncology · 2022Article
- Consideration of Metabolite Efflux in Radiolabelled Choline Kinetics.Pharmaceutics · 2021Article
- Replication of GWAS significant loci in a sub-Saharan African Cohort with early childhood caries: a pilot study.BMC oral health · 2021Article
- Choline supplementation prevents the effects of bilirubin on cerebellar-mediated behavior in choline-restricted Gunn rat pups.Pediatric research · 2021Article
- Choline and Folic Acid in Diets Consumed during Pregnancy Interact to Program Food Intake and Metabolic Regulation of Male Wistar Rat Offspring.The Journal of nutrition · 2021Article
- Genetic diseases of the Kennedy pathways for membrane synthesis.The Journal of biological chemistry · 2020Review
- Choline ameliorates ethanol induced alterations in tyrosine phosphorylation and distribution in detergent-resistant membrane microdomains of L1 cell adhesion molecule in vivo.Birth defects research · 2020Article
- Article
- Targeted metabolomics for serum amino acids and acylcarnitines in patients with lung cancer.Experimental and therapeutic medicine · 2019Article
- Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe Kennedy pathway generates phosphocoline and phosphoethanolamine through its two branches. Choline Kinase (ChoK) is the first enzyme of the Kennedy branch of synthesis of phosphocholine, the major component of the plasma membrane. ChoK family of proteins is composed by ChoKalpha and ChoKbeta isoforms, the first one with two different variants of splicing. Recently ChoKalpha has been implicated in the carcinogenic process, since it is over-expressed in a variety of human cancers. However, no evidence for a role of ChoKbeta in carcinogenesis has been reported. METHODOLOGY/PRINCIPAL
findingsHere we compare the in vitro and in vivo properties of ChoKalpha1 and ChoKbeta in lipid metabolism, and their potential role in carcinogenesis. Both ChoKalpha1 and ChoKbeta showed choline and ethanolamine kinase activities when assayed in cell extracts, though with different affinity for their substrates. However, they behave differentially when overexpressed in whole cells. Whereas ChoKbeta display an ethanolamine kinase role, ChoKalpha1 present a dual choline/ethanolamine kinase role, suggesting the involvement of each ChoK isoform in distinct biochemical pathways under in vivo conditions. In addition, while overexpression of ChoKalpha1 is oncogenic when overexpressed in HEK293T or MDCK cells, ChoKbeta overexpression is not sufficient to induce in vitro cell transformation nor in vivo tumor growth. Furthermore, a significant upregulation of ChoKalpha1 mRNA levels in a panel of breast and lung cancer cell lines was found, but no changes in ChoKbeta mRNA levels were observed. Finally, MN58b, a previously described potent inhibitor of ChoK with in vivo antitumoral activity, shows more than 20-fold higher efficiency towards ChoKalpha1 than ChoKbeta. CONCLUSION/SIGNIFICANCE: This study represents the first evidence of the distinct metabolic role of ChoKalpha and ChoKbeta isoforms, suggesting different physiological roles and implications in human carcinogenesis. These findings constitute a step forward in the design of an antitumoral strategy based on ChoK inhibition.
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