ArticleCell death and differentiation2015
The Fcp1-Wee1-Cdk1 axis affects spindle assembly checkpoint robustness and sensitivity to antimicrotubule cancer drugs.
Article in Cell death and differentiation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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Who cites it
29 citing papers in PubMed, 50 citations in OpenAlex.
- PKMYT1 has an important role in the timing and fidelity of chromosome segregation.EMBO reports · 2026Article
- Identification and Characterization of a NovelInternational journal of molecular sciences · 2024Article
- Sequential drug treatment targeting cell cycle and cell fate regulatory programs blocks non-genetic cancer evolution in acute lymphoblastic leukemia.Genome biology · 2024Article
- Chromosome alignment and Kif18A action rely on spindle-localized control of Cdk1 activity.Frontiers in cell and developmental biology · 2024Article
- Targeted inhibition of the methyltransferase SETD8 synergizes with the Wee1 inhibitor adavosertib in restraining glioblastoma growth.Cell death & disease · 2023Article
- Myt1 overexpression mediates resistance to cell cycle and DNA damage checkpoint kinase inhibitors.Frontiers in cell and developmental biology · 2023Article
- Article
- Uncoupling of Mitosis and Cytokinesis Upon a Prolonged Arrest in Metaphase Is Influenced by Protein Phosphatases and Mitotic Transcription in Fission Yeast.Frontiers in cell and developmental biology · 2022Article
- WEE1 Inhibitor: Clinical Development.Current oncology reports · 2021Review
- Article
- Small Molecules Targeting Biological Clock; A Novel Prospective for Anti-Cancer Drugs.Molecules (Basel, Switzerland) · 2020Review
- A WEE1 family business: regulation of mitosis, cancer progression, and therapeutic target.Journal of hematology & oncology · 2020Review
- Antitumor effect of a WEE1 inhibitor and potentiation of olaparib sensitivity by DNA damage response modulation in triple-negative breast cancer.Scientific reports · 2020Article
- Exploiting immune-dependent effects of microtubule-targeting agents to improve efficacy and tolerability of cancer treatment.Cell death & disease · 2020Review
- Recent advances in understanding the role of Cdk1 in the Spindle Assembly Checkpoint.F1000Research · 2020Review
- 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
- Wee1 Rather Than Plk1 Is Inhibited by AZD1775 at Therapeutically Relevant Concentrations.Cancers · 2019Article
- MicroRNA-155 controls vincristine sensitivity and predicts superior clinical outcome in diffuse large B-cell lymphoma.Blood advances · 2019Article
- Imbalance of the spindle-assembly checkpoint promotes spindle poison-mediated cytotoxicity with distinct kinetics.Cell death & disease · 2019Article
- Inhibiting Wee1 and ATR kinases produces tumor-selective synthetic lethality and suppresses metastasis.The Journal of clinical investigation · 2019Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To grant faithful chromosome segregation, the spindle assembly checkpoint (SAC) delays mitosis exit until mitotic spindle assembly. An exceedingly prolonged mitosis, however, promotes cell death and by this means antimicrotubule cancer drugs (AMCDs), that impair spindle assembly, are believed to kill cancer cells. Despite malformed spindles, cancer cells can, however, slip through SAC, exit mitosis prematurely and resist killing. We show here that the Fcp1 phosphatase and Wee1, the cyclin B-dependent kinase (cdk) 1 inhibitory kinase, play a role for this slippage/resistance mechanism. During AMCD-induced prolonged mitosis, Fcp1-dependent Wee1 reactivation lowered cdk1 activity, weakening SAC-dependent mitotic arrest and leading to mitosis exit and survival. Conversely, genetic or chemical Wee1 inhibition strengthened the SAC, further extended mitosis, reduced antiapoptotic protein Mcl-1 to a minimum and potentiated killing in several, AMCD-treated cancer cell lines and primary human adult lymphoblastic leukemia cells. Thus, the Fcp1-Wee1-Cdk1 (FWC) axis affects SAC robustness and AMCDs sensitivity.
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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.