ArticleOncogene2004
Choline kinase inhibition induces the increase in ceramides resulting in a highly specific and selective cytotoxic antitumoral strategy as a potential mechanism of action.
Article in Oncogene, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
41 citing papers in PubMed, 91 citations in OpenAlex.
- Enzymes of sphingolipid metabolism as transducers of metabolic inputs.Biochemical Society transactions · 2024Review
- Inhibition of choline metabolism in an angioimmunoblastic T-cell lymphoma preclinical model reveals a new metabolic vulnerability as possible target for treatment.Journal of experimental & clinical cancer research : CR · 2024Article
- Is choline kinase alpha a drug target for obesity?Frontiers in endocrinology · 2024Article
- Mining Fatty Acid Biosynthesis for New Antimicrobials.Annual review of microbiology · 2022Review
- VEGF Overexpression Significantly Increases Nanoparticle-Mediated siRNA Delivery and Target-Gene Downregulation.Pharmaceutics · 2022Article
- Choline Kinase α Inhibitors MN58b and RSM932A Enhances the Antitumor Response to Cisplatin in Lung Tumor Cells.Pharmaceutics · 2022Article
- Biological Evaluation of New Thienopyridinium and Thienopyrimidinium Derivatives as Human Choline Kinase Inhibitors.Pharmaceutics · 2022Article
- Anticancer and Structure Activity Relationship of Non-Symmetrical Choline Kinase Inhibitors.Pharmaceutics · 2021Article
- ChoK-Full of Potential: Choline Kinase in B Cell and T Cell Malignancies.Pharmaceutics · 2021Review
- Choline Kinase: An Unexpected Journey for a Precision Medicine Strategy in Human Diseases.Pharmaceutics · 2021Review
- The Heterogeneity of Breast Cancer Metabolism.Advances in experimental medicine and biology · 2021Article
- Article
- Near infrared fluorescent imaging of choline kinase alpha expression and inhibition in breast tumors.Oncotarget · 2017Article
- Overexpression of CHKA contributes to tumor progression and metastasis and predicts poor prognosis in colorectal carcinoma.Oncotarget · 2016Article
- Choline kinase alpha-Putting the ChoK-hold on tumor metabolism.Progress in lipid research · 2016Review
- The novel choline kinase inhibitor ICL-CCIC-0019 reprograms cellular metabolism and inhibits cancer cell growth.Oncotarget · 2016Article
- Increased activity of CHK enhances the radioresistance of MCF-7 breast cancer stem cells.Oncology letters · 2015Article
- Choline metabolism-based molecular diagnosis of cancer: an update.Expert review of molecular diagnostics · 2015Review
- Magnetic resonance spectroscopy for detection of choline kinase inhibition in the treatment of brain tumors.Molecular cancer therapeutics · 2015Article
- A new family of choline kinase inhibitors with antiproliferative and antitumor activity derived from natural products.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2015Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Choline kinase (ChoK, E.C. 2.7.1.32) is involved in the synthesis of phosphatidylcholine (PC), and has been found to be increased in human tumors and tumor-derived cell lines. Furthermore, ChoK inhibitors have been reported to show a potent and selective antitumoral activity both in vitro and in vivo. Here, we provide the basis for a rational understanding of the antitumoral activity of ChoK inhibitors. In normal cells, blockage of de novo phosphorylcholine (PCho) synthesis by inhibition of ChoK promotes the dephosphorylation of pRb, resulting in a reversible cell cycle arrest at G0/G1 phase. In contrast, ChoK inhibition in tumor cells renders cells unable to arrest in G0/G1 as manifested by a lack of pRb dephosphorylation. Furthermore, tumor cells specifically suffer a drastic wobble in the metabolism of main membrane lipids PC and sphingomyelin (SM). This lipid disruption results in the enlargement of the intracellular levels of ceramides. As a consequence, normal cells remain unaffected, but tumor cells are promoted to apoptosis. Thus, we provide in this study the rationale for the potential clinical use of ChoK inhibitors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.