ArticleNature communications2016
Comprehensive functional analysis of the tousled-like kinase 2 frequently amplified in aggressive luminal breast cancers.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
What it found
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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.
The trial behind it
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
50 citing papers in PubMed, 73 citations in OpenAlex.
- Co-Phosphoregulatory Network Underlying Functional Coherence of TLK1 and TLK2 Kinase Paralogs.International journal of molecular sciences · 2026Article
- NPM1 Mediates mRNA Sorting into Extracellular Vesicles via Specific RNA Motif Binding and Phase Separation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Calcium overload induced mitochondrial and lysosomal dysfunction is regulated by Tousled-like kinase in a-synucleinopathy.Cell death & disease · 2026Article
- Neuronal differentiation and activity drive nucleocytoplasmic shuttling of the intellectual disability kinase TLK2.Frontiers in cellular neuroscience · 2026Article
- Targeting TLK2 with antisense oligonucleotides as a new strategy in acute myeloid leukemia.Frontiers in oncology · 2026Article
- Beyond COL1A1::PDGFB: Rare fusions and their clinical implications in dermatofibrosarcoma protuberans.World journal of clinical cases · 2025Article
- Chromatin looping-based CRISPR screen identifies TLK2 as chromatin loop formation regulator in cancer stemness plasticity.Nature communications · 2025Article
- A TLK2-mediated calcium-driven cell death pathway links neuronal degeneration to nuclear envelope disruption.Nature communications · 2025Article
- Article
- Autophosphorylation of the Tousled-like kinases TLK1 and TLK2 regulates recruitment to damaged chromatin via PCNA interaction.Nucleic acids research · 2025Article
- Tousled-like kinase loss confers PARP inhibitor resistance in BRCA1-mutated cancers by impeding non-homologous end joining repair.Molecular medicine (Cambridge, Mass.) · 2025Article
- Beyond the Horizon: Rethinking Prostate Cancer Treatment Through Innovation and Alternative Strategies.Cancers · 2024Article
- Article
- The TLK-ASF1 histone chaperone pathway plays a critical role in IL-1β-mediated AML progression.Blood · 2024Article
- Noninvasive assessment of organ-specific and shared pathways in multi-organ fibrosis using T1 mapping.Nature medicine · 2024Article
- Discovery and optimization of narrow spectrum inhibitors of Tousled like kinase 2 (TLK2) using quantitative structure activity relationships.European journal of medicinal chemistry · 2024Article
- Autophosphorylation of the Tousled-like kinases TLK1 and TLK2 regulates recruitment to damaged chromatin via PCNA interaction.bioRxiv : the preprint server for biology · 2024Article
- Discovery and Optimization of Narrow Spectrum Inhibitors of Tousled Like Kinase 2 (TLK2) Using Quantitative Structure Activity Relationships.bioRxiv : the preprint server for biology · 2023Article
- Review
- Targeting TLK2 inhibits the progression of gastric cancer by reprogramming amino acid metabolism through the mTOR/ASNS axis.Cancer gene therapy · 2023Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
More aggressive and therapy-resistant oestrogen receptor (ER)-positive breast cancers remain a great clinical challenge. Here our integrative genomic analysis identifies tousled-like kinase 2 (TLK2) as a candidate kinase target frequently amplified in ∼10.5% of ER-positive breast tumours. The resulting overexpression of TLK2 is more significant in aggressive and advanced tumours, and correlates with worse clinical outcome regardless of endocrine therapy. Ectopic expression of TLK2 leads to enhanced aggressiveness in breast cancer cells, which may involve the EGFR/SRC/FAK signalling. Conversely, TLK2 inhibition selectively inhibits the growth of TLK2-high breast cancer cells, downregulates ERα, BCL2 and SKP2, impairs G1/S cell cycle progression, induces apoptosis and significantly improves progression-free survival in vivo. We identify two potential TLK2 inhibitors that could serve as backbones for future drug development. Together, amplification of the cell cycle kinase TLK2 presents an attractive genomic target for aggressive ER-positive breast cancers.
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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 Socratic graph.