ArticleNature medicine2011
Kinome screening for regulators of the estrogen receptor identifies LMTK3 as a new therapeutic target in breast cancer.
Article in Nature medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 135 citations in OpenAlex.
- Article
- Unlocking the ferroptotic window: Lipidomic rewiring and metabolic addiction in EMT-driven breast cancer resistance.Cell death discovery · 2026Review
- LMTK3 as a spatially regulated and stage-dependent biomarker in epithelial ovarian tumorigenesis.Molecular therapy. Oncology · 2026Article
- LMTK3 regulates breast cancer angiogenesis via a context-dependent mesenchymal-epithelial transition program.Cancer gene therapy · 2026Article
- Integrative analysis of lysosome-dependent cell death related molecular subtypes and prognosis prediction in papillary thyroid carcinoma.Journal of Cancer · 2026Article
- Evaluation of the Association between LMTK3 Gene Polymorphism and Breast Cancer Risk in the Indian Population.Asian Pacific journal of cancer prevention : APJCP · 2025Article
- LMTK3 regulation of EV biogenesis and cargo sorting promotes tumour growth by reducing monocyte infiltration and driving pro-tumourigenic macrophage polarisation in breast cancer.Molecular cancer · 2025Article
- The lemur tail kinase family in neuronal function and disfunction in neurodegenerative diseases.Cellular and molecular life sciences : CMLS · 2024Review
- Transcriptomic analysis of the 12 major human breast cell types reveals mechanisms of cell and tissue function.PLoS biology · 2024Article
- Lemur tail kinase 3 serves as a predictor of patient outcomes and a target for the treatment of ovarian cancer.Molecular therapy. Oncology · 2024Article
- The brain-specific kinase LMTK3 regulates neuronal excitability by decreasing KCC2-dependent neuronal CliScience · 2024Article
- Kinome-Wide Synthetic Lethal Screen Identifies PANK4 as a Modulator of Temozolomide Resistance in Glioblastoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- KIT mutations and expression: current knowledge and new insights for overcoming IM resistance in GIST.Cell communication and signaling : CCS · 2024Review
- A revised nomenclature for the lemur family of protein kinases.Communications biology · 2024Review
- Chemoinformatics and machine learning techniques to identify novel inhibitors of the lemur tyrosine kinase-3 receptor involved in breast cancer.Frontiers in molecular biosciences · 2024Article
- Integrated multi-omics approach to distinct molecular characterization and classification of early-onset colorectal cancer.Cell reports. Medicine · 2023Article
- Developmental programming: Adipose depot-specific regulation of non-coding RNAs and their relation to coding RNA expression in prenatal testosterone and prenatal bisphenol-A -treated female sheep.Molecular and cellular endocrinology · 2023Article
- The Inhibitory Properties of a Novel, Selective LMTK3 Kinase Inhibitor.International journal of molecular sciences · 2023Article
- The Rattlesnake W Chromosome: A GC-Rich Retroelement Refugium with Retained Gene Function Across Ancient Evolutionary Strata.Genome biology and evolution · 2022Article
- Anastrozole Regulates Fatty Acid Synthase in Breast Cancer.Molecular cancer therapeutics · 2022Article
20 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
Therapies targeting estrogen receptor α (ERα, encoded by ESR1) have transformed the treatment of breast cancer. However, large numbers of women relapse, highlighting the need for the discovery of new regulatory targets modulating ERα pathways. An siRNA screen identified kinases whose silencing alters the estrogen response including those previously implicated in regulating ERα activity (such as mitogen-activated protein kinase and AKT). Among the most potent regulators was lemur tyrosine kinase-3 (LMTK3), for which a role has not previously been assigned. In contrast to other modulators of ERα activity, LMTK3 seems to have been subject to Darwinian positive selection, a noteworthy result given the unique susceptibility of humans to ERα+ breast cancer. LMTK3 acts by decreasing the activity of protein kinase C (PKC) and the phosphorylation of AKT (Ser473), thereby increasing binding of forkhead box O3 (FOXO3) to the ESR1 promoter. LMTK3 phosphorylated ERα, protecting it from proteasomal degradation in vitro. Silencing of LMTK3 reduced tumor volume in an orthotopic mouse model and abrogated proliferation of ERα+ but not ERα- cells, indicative of its role in ERα activity. In human cancers, LMTK3 abundance and intronic polymorphisms were significantly associated with disease-free and overall survival and predicted response to endocrine therapies. These findings yield insights into the natural history of breast cancer in humans and reveal LMTK3 as a new therapeutic target.
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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.