ArticleBreast cancer research and treatment2021
N-myristoyltransferase proteins in breast cancer: prognostic relevance and validation as a new drug target.
Article in Breast cancer research and treatment, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 25 citations in OpenAlex.
- N-Myristoyltransferase 2 Is Regulated by Polyphosphate-Driven Lysine Interactions.Biomolecules · 2026Article
- Processes and therapeutic perspectives of acylation modifications of lysine and cysteine in tumors.Cell communication and signaling : CCS · 2026Review
- Pharmacological Myristoylation Inhibition by Zelenirstat Disrupts Growth Signalling, Energy Metabolism, and Migration in Triple-Negative Breast Cancer Cells.Breast cancer (Dove Medical Press) · 2026Article
- Post-translational modifications at the crossroads of cancer metabolism and immune regulation: therapeutic opportunities and challenges.International journal of surgery (London, England) · 2026Review
- Collateral metabolic vulnerabilities unveiled by loss of isozyme diversity in breast cancer.Genome medicine · 2025Article
- Intracellular Peptide N-Myristoylation for Cancer Cell Ferroptosis without Acquired Resistance.Journal of the American Chemical Society · 2025Article
- Targeting Src tyrosine kinase to enhance radioiodide uptake in breast cancer.Endocrine-related cancer · 2025Article
- Protein lipidation in the tumor microenvironment: enzymology, signaling pathways, and therapeutics.Molecular cancer · 2025Review
- A first-in-human phase I trial of daily oral zelenirstat, a N-myristoyltransferase inhibitor, in patients with advanced solid tumors and relapsed/refractory B-cell lymphomas.Investigational new drugs · 2024Article
- Multiomics analysis identifies oxidative phosphorylation as a cancer vulnerability arising from myristoylation inhibition.Journal of translational medicine · 2024Article
- Protein lipidation in cancer: mechanisms, dysregulation and emerging drug targets.Nature reviews. Cancer · 2024Review
- The role of N-myristoyltransferase 1 in tumour development.Annals of medicine · 2023Review
- Tackling Sleeping Sickness: Current and Promising Therapeutics and Treatment Strategies.International journal of molecular sciences · 2023Review
- Impact of Protein NLife (Basel, Switzerland) · 2023Review
- SPI1 Mediates N-Myristoyltransferase 1 to Advance Gastric Cancer Progression via PI3K/AKT/mTOR Pathway.Canadian journal of gastroenterology & hepatology · 2023Article
- The Exposure to Human Breast Cancer Cells Altered 14 Post-Translational Modifications of Human Serum Albumin.EJIFCC · 2022Article
- Post-Translational Modifications by Lipid Metabolites during the DNA Damage Response and Their Role in Cancer.Biomolecules · 2022Review
- Novel, First-in-Human, Oral PCLX-001 Treatment in a Patient with Relapsed Diffuse Large B-Cell Lymphoma.Current oncology (Toronto, Ont.) · 2022Article
- MicroRNA 132-3p Is Upregulated in Laron Syndrome Patients and Controls Longevity Gene Expression.International journal of molecular sciences · 2021Article
- Protein Lipidation by Palmitoylation and Myristoylation in Cancer.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
purposeN-myristoyltransferases 1 and 2 (NMT1 and NMT2) catalyze the addition of 14-carbon fatty acids to the N-terminus of proteins. Myristoylation regulates numerous membrane-bound signal transduction pathways important in cancer biology and the pan-NMT inhibitor PCLX-001 is approaching clinical development as a cancer therapy. The tissue distribution, relative abundances, and prognostic value of the two human NMTs remain poorly understood.
methodsWe generated and validated mutually exclusive monoclonal antibodies (mAbs) specific to human NMT1 and NMT2. These mAbs were used to perform immunohistochemical analysis of the abundance and distribution of NMT1 and NMT2 in normal breast epithelial samples and a large cohort of primary breast adenocarcinomas from the BCIRG001 clinical trial (n = 706).
resultsNMT1 protein was readily quantified in normal and most transformed breast epithelial tissue and was associated with higher overall histologic grade, higher Ki67, and lower hormone receptor expression. While NMT2 protein was readily detected in normal breast epithelial tissue, it was undetectable in the majority of breast cancers. Detectable NMT2 protein correlated with significantly poorer overall survival (hazard ratio 1.36; P = 0.029) and worse biological features including younger age, higher histologic grade, lower hormone receptor expression, higher Ki67, and p53 positivity. Treatment of cultured breast cancer cells with PCLX-001 reduced cell viability in vitro. Daily oral administration of PCLX-001 to immunodeficient mice bearing human MDA-MB-231 breast cancer xenografts produced significant dose-dependent tumor growth inhibition in vivo.
conclusionsThese results support further evaluation of NMT immunohistochemistry for patient selection and clinical trials of NMT inhibition in breast cancer patients.
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