ArticleBreast cancer research : BCR2012
Small interfering RNA library screen identified polo-like kinase-1 (PLK1) as a potential therapeutic target for breast cancer that uniquely eliminates tumor-initiating cells.
Article in Breast cancer research : BCR, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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45 citing papers in PubMed, 88 citations in OpenAlex.
- Integrated single-cell and spatial mapping coupled with machine learning unveils core stemness landscapes and regulatory drivers in triple-negative breast cancer.Discover oncology · 2026Article
- Advances in siRNA Drug Delivery Strategies for Targeted TNBC Therapy.Bioengineering (Basel, Switzerland) · 2024Review
- Dual TTK/PLK1 inhibition has potent anticancer activity in TNBC as monotherapy and in combination.Frontiers in oncology · 2024Article
- Article
- Identification of novel inhibitors from Urtica spp against TNBC targeting JAK2 receptor for breast cancer therapy.Medical oncology (Northwood, London, England) · 2023Article
- RPL27 contributes to colorectal cancer proliferation and stemness via PLK1 signaling.International journal of oncology · 2023Article
- Development of hyaluronic acid-anchored polycaprolactone nanoparticles for efficient delivery of PLK1 siRNA to breast cancer.Drug delivery and translational research · 2023Article
- Genetic heterogeneity of liver cancer stem cells.Anatomy & cell biology · 2023Article
- Article
- HN1L/AP-2γ/PLK1 signaling drives tumor progression and chemotherapy resistance in esophageal squamous cell carcinoma.Cell death & disease · 2022Article
- A Novel Allosteric Inhibitor Targets PLK1 in Triple Negative Breast Cancer Cells.Biomolecules · 2022Article
- Bioinformatics analysis of key genes in triple negative breast cancer and validation of oncogene PLK1.Annals of translational medicine · 2020Article
- The CINs of Polo-Like Kinase 1 in Cancer.Cancers · 2020Review
- Bioengineered siRNA-Based Nanoplatforms Targeting Molecular Signaling Pathways for the Treatment of Triple Negative Breast Cancer: Preclinical and Clinical Advancements.Pharmaceutics · 2020Review
- Phosphorus Dendrimers as Nanotools against Cancers.Molecules (Basel, Switzerland) · 2020Review
- Identification of key genes controlling breast cancer stem cell characteristics via stemness indices analysis.Journal of translational medicine · 2020Article
- Target Analysis and Mechanism of Podophyllotoxin in the Treatment of Triple-Negative Breast Cancer.Frontiers in pharmacology · 2020Article
- PLK1 and EGFR targeted nanoparticle as a radiation sensitizer for non-small cell lung cancer.Cancer letters · 2019Article
- MCC1019, a selective inhibitor of the Polo-box domain of Polo-like kinase 1 as novel, potent anticancer candidate.Acta pharmaceutica Sinica. B · 2019Article
- Therapeutic potential of PLK1 inhibition in triple-negative breast cancer.Laboratory investigation; a journal of technical methods and pathology · 2019Article
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4 authors at 2 institutions in 1 country.
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Abstract
introductionTriple-negative breast cancer (TNBC) high rate of relapse is thought to be due to the presence of tumor-initiating cells (TICs), molecularly defined as being CD44high/CD24-/low. TICs are resilient to chemotherapy and radiation. However, no currently accepted molecular target exists against TNBC and, moreover, TICs. Therefore, we sought the identification of kinase targets that inhibit TNBC growth and eliminate TICs.
methodsA genome-wide human kinase small interfering RNA (siRNA) library (691 kinases) was screened against the TNBC cell line SUM149 for growth inhibition. Selected siRNAs were then tested on four different breast cancer cell lines to confirm the spectrum of activity. Their effect on the CD44high subpopulation and sorted CD44high/CD24-/low cells of SUM149 also was studied. Further studies were focused on polo-like kinase 1 (PLK1), including its expression in breast cancer cell lines, effect on the CD44high/CD24-/low TIC subpopulation, growth inhibition, mammosphere formation, and apoptosis, as well as the activity of the PLK1 inhibitor, BI 2536.
resultsOf the 85 kinases identified in the screen, 28 of them were further silenced by siRNAs on MDA-MB-231 (TNBC), BT474-M1 (ER+/HER2+, a metastatic variant), and HR5 (ER+/HER2+, a trastuzumab-resistant model) cells and showed a broad spectrum of growth inhibition. Importantly, 12 of 28 kinases also reduced the CD44high subpopulation compared with control in SUM149. Further tests of these 12 kinases directly on a sorted CD44high/CD24-/low TIC subpopulation of SUM149 cells confirmed their effect. Blocking PLK1 had the greatest growth inhibition on breast cancer cells and TICs by about 80% to 90% after 72 hours. PLK1 was universally expressed in breast cancer cell lines, representing all of the breast cancer subtypes, and was positively correlated to CD44. The PLK1 inhibitor BI 2536 showed similar effects on growth, mammosphere formation, and apoptosis as did PLK1 siRNAs. Finally, whereas paclitaxel, doxorubicin, and 5-fluorouracil enriched the CD44high/CD24-/low population compared with control in SUM149, subsequent treatment with BI 2536 killed the emergent population, suggesting that it could potentially be used to prevent relapse.
conclusionInhibiting PLK1 with siRNA or BI 2536 blocked growth of TNBCs including the CD44high/CD24-/low TIC subpopulation and mammosphere formation. Thus, PLK1 could be a potential therapeutic target for the treatment of TNBC as well as other subtypes of breast cancer.
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