ArticleOncogenesis2020
LIMK2 promotes the metastatic progression of triple-negative breast cancer by activating SRPK1.
Article in Oncogenesis, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 2 of them syntheses that pooled it.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 2 syntheses or guidelines pooled it, 43 citations in OpenAlex.
- Serine-Arginine Protein Kinase 1 (SRPK1): a systematic review of its multimodal role in oncogenesis.Molecular and cellular biochemistry · 2022Pooled it
- FOXP4-AS1 May be a Potential Prognostic Biomarker in Human Cancers: A Meta-Analysis and Bioinformatics Analysis.Frontiers in oncology · 2022Pooled it
- Ift46 deficiency causes renal cyst via enhanced Limk2 through lack of autophagy flux.Cell communication and signaling : CCS · 2026Article
- LIMK2 promotes centrosome clustering and cancer progression by activating MST4-mediated phosphorylation of NPM1.Oncogene · 2025Article
- Tetrahydropyrazolopyridinones as a Novel Class of Potent and Highly Selective LIMK Inhibitors.Journal of medicinal chemistry · 2025Article
- Alternative Splicing: A Critical Regulator in Human Bone Biology and Tumor Progression.Research (Washington, D.C.) · 2025Review
- KLF7 enhances the inflammatory response in LPS-induced alveolar epithelial cellsCentral-European journal of immunology · 2025Article
- NCellular & molecular biology letters · 2024Article
- SRPK1 Promotes Glioma Proliferation, Migration, and Invasion through Activation of Wnt/β-Catenin and JAK-2/STAT-3 Signaling Pathways.Biomedicines · 2024Article
- LIM kinases in cardiovascular health and disease.Frontiers in physiology · 2024Review
- Gene Signature Associated with Nervous System in an Experimental Radiation- and Estrogen-Induced Breast Cancer Model.Biomedicines · 2023Article
- SRPKs: a promising therapeutic target in cancer.Clinical and experimental medicine · 2023Review
- Suppresses of LIM kinase 2 promotes radiosensitivity in radioresistant non-small cell lung cancer cells.Heliyon · 2023Article
- Review
- Alternative Splicing Events and Their Clinical Significance in Colorectal Cancer: Targeted Therapeutic Opportunities.Cancers · 2023Review
- LIMK2: A Multifaceted kinase with pleiotropic roles in human physiology and pathologies.Cancer letters · 2023Review
- The identification of a two-gene prognostic model based on cisplatin resistance-related ceRNA network in small cell lung cancer.BMC medical genomics · 2023Article
- LIMK2 promotes melanoma tumor growth and metastasis through G3BP1-ESM1 pathway-mediated apoptosis inhibition.Oncogene · 2023Article
- SRSF5 Regulates the Expression of BQ323636.1 to Modulate Tamoxifen Resistance in ER-Positive Breast Cancer.Cancers · 2023Article
- LIM Kinases, LIMK1 and LIMK2, Are Crucial Node Actors of the Cell Fate: Molecular to Pathological Features.Cells · 2023Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Triple-negative breast cancer (TNBC) is a highly metastatic breast cancer subtype and due to the lack of hormone receptors and HER2 expression, TNBC has limited therapeutic options with chemotherapy being the primary choice for systemic therapy. LIM Domain Kinase 2 (LIMK2) is a serine/threonine kinase that plays an important role in the regulation of actin filament dynamics. Here, we show that LIM domain kinase 2 (LIMK2) is overexpressed in TNBC, and short-hairpin RNA (shRNA)-mediated LIMK2 knockdown or its pharmacological inhibition blocks metastatic attributes of TNBC cells. To determine the mechanism by which LIMK2 promotes TNBC metastatic progression, we performed stable isotope labeling by amino acids in cell culture (SILAC) based unbiased large-scale phosphoproteomics analysis. This analysis identified 258 proteins whose phosphorylation was significantly reduced due to LIMK2 inhibition. Among these proteins, we identified SRSF protein kinase 1 (SRPK1), which encodes for a serine/arginine protein kinase specific for the SR (serine/arginine-rich domain) family of splicing factors. We show that LIMK2 inhibition blocked SRPK1 phosphorylation and consequentially its activity. Furthermore, similar to LIMK2, genetic inhibition of SRPK1 by shRNAs or its pharmacological inhibition blocked the metastatic attributes of TNBC cells. Moreover, the pharmacological inhibition of LIMK2 blocked metastatic progression in mice without affecting primary tumor growth. In sum, these results identified LIMK2 as a facilitator of distal TNBC metastasis and a potential target for preventing TNBC metastatic progression.
Identifiers
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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.