ArticleOncotarget2017
Prolonged mitotic arrest induced by Wee1 inhibition sensitizes breast cancer cells to paclitaxel.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 54 citations in OpenAlex.
- HTSplotter: An end-to-end data processing, analysis and visualisation tool for chemical and genetic in vitro perturbation screening.PloS one · 2024Article
- Article
- WEE1 Inhibitors Mediate Antitumor Effects on Endometrial Cancer through Activation of Innate Immune Responses.Journal of Cancer · 2024Article
- Unleashing the Power of Synthetic Lethality: Augmenting Treatment Efficacy through Synergistic Integration with Chemotherapy Drugs.Pharmaceutics · 2023Review
- Myt1 overexpression mediates resistance to cell cycle and DNA damage checkpoint kinase inhibitors.Frontiers in cell and developmental biology · 2023Article
- Interrogating the Genomic Landscape of Uterine Leiomyosarcoma: A Potential for Patient Benefit.Cancers · 2022Review
- Cell Synchronization Techniques for Studying Mitosis.Methods in molecular biology (Clifton, N.J.) · 2022Article
- DNA damage response and GATA4 signaling in cellular senescence and aging-related pathology.Frontiers in aging neuroscience · 2022Review
- Targeting the DNA Damage Response for Cancer Therapy by Inhibiting the Kinase Wee1.Frontiers in oncology · 2022Review
- WEE1 Inhibitor: Clinical Development.Current oncology reports · 2021Review
- Facilitating Drug Discovery in Breast Cancer by Virtually Screening Patients Using In Vitro Drug Response Modeling.Cancers · 2021Article
- Modeling Heterogeneity of Triple-Negative Breast Cancer Uncovers a Novel Combinatorial Treatment Overcoming Primary Drug Resistance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Article
- A WEE1 family business: regulation of mitosis, cancer progression, and therapeutic target.Journal of hematology & oncology · 2020Review
- Wee1 kinase inhibitor AZD1775 potentiates CD8+ T cell-dependent antitumour activity via dendritic cell activation following a single high dose of irradiation.Medical oncology (Northwood, London, England) · 2020Article
- The cGAS/STING/TBK1/IRF3 innate immunity pathway maintains chromosomal stability through regulation of p21 levels.Experimental & molecular medicine · 2020Article
- WEE1 inhibition synergizes with CHOP chemotherapy and radiation therapy through induction of premature mitotic entry and DNA damage in diffuse large B-cell lymphoma.Therapeutic advances in hematology · 2020Article
- A Tyrosine Kinase Expression Signature Predicts the Post-Operative Clinical Outcome in Triple Negative Breast Cancers.Cancers · 2019Article
- Inhibiting Wee1 and ATR kinases produces tumor-selective synthetic lethality and suppresses metastasis.The Journal of clinical investigation · 2019Article
- Wee1 Inhibitor AZD1775 Effectively Inhibits the Malignant Phenotypes of Esophageal Squamous Cell CarcinomaFrontiers in pharmacology · 2019Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Wee1 kinase is a crucial negative regulator of Cdk1/cyclin B1 activity and is required for normal entry into and exit from mitosis. Wee1 activity can be chemically inhibited by the small molecule MK-1775, which is currently being tested in phase I/II clinical trials in combination with other anti-cancer drugs. MK-1775 promotes cancer cells to bypass the cell-cycle checkpoints and prematurely enter mitosis. In our study, we show premature mitotic cells that arise from MK-1775 treatment exhibited centromere fragmentation, a morphological feature of mitotic catastrophe that is characterized by centromeres and kinetochore proteins that co-cluster away from the condensed chromosomes. In addition to stimulating early mitotic entry, MK-1775 treatment also delayed mitotic exit. Specifically, cells treated with MK-1775 following release from G1/S or prometaphase arrested in mitosis. MK-1775 induced arrest occurred at metaphase and thus, cells required 12 times longer to transition into anaphase compared to controls. Consistent with an arrest in mitosis, MK-1775 treated prometaphase cells maintained high cyclin B1 and low phospho-tyrosine 15 Cdk1. Importantly, MK-1775 induced mitotic arrest resulted in cell death regardless the of cell-cycle phase prior to treatment suggesting that Wee1 inhibitors are also anti-mitotic agents. We found that paclitaxel enhances MK-1775 mediated cell killing. HeLa and different breast cancer cell lines (T-47D, MCF7, MDA-MB-468 and MDA-MB-231) treated with different concentrations of MK-1775 and low dose paclitaxel exhibited reduced cell survival compared to mono-treatments. Our data highlight a new potential strategy for enhancing MK-1775 mediated cell killing in breast cancer cells.
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Registered trials
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