ArticlePloS one2013
Cdk4 and nek2 signal binucleation and centrosome amplification in a her2+ breast cancer model.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 43 citations in OpenAlex.
- NEK2 drives pathogenesis, drug resistance, and LMP1 expression in EBV-positive non-Hodgkin lymphoma.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Endogenous and environmental factors that induce DNA replication defects and genomic instability in ER-negative heterozygous BRCA1 cells.Scientific reports · 2026Article
- Overexpressed NEK2 contributes to progression and cisplatin resistance through activating the Wnt/β-catenin signaling pathway in cervical cancer.Cancer cell international · 2025Article
- Mitotic kinases are emerging therapeutic targets against metastatic breast cancer.Cell division · 2024Review
- Inhibition of NEK2 Promotes Chemosensitivity and Reduces KSHV-positive Primary Effusion Lymphoma Burden.Cancer research communications · 2024Article
- Bifunctional Inhibitor Reveals NEK2 as a Therapeutic Target and Regulator of Oncogenic Pathways in Lymphoma.Molecular cancer therapeutics · 2024Article
- Centrosomes and associated proteins in pathogenesis and treatment of breast cancer.Frontiers in oncology · 2024Review
- Ethnic and racial-specific differences in levels of centrosome-associated mitotic kinases, proliferative and epithelial-to-mesenchymal markers in breast cancers.Cell division · 2022Article
- Nek2 Kinase Signaling in Malaria, Bone, Immune and Kidney Disorders to Metastatic Cancers and Drug Resistance: Progress on Nek2 Inhibitor Development.Molecules (Basel, Switzerland) · 2022Review
- Silencing of Nek2 suppresses the proliferation, migration and invasion and induces apoptosis of breast cancer cells by regulating ERK/MAPK signaling.Journal of molecular histology · 2021Article
- Mitotic kinases as drivers of the epithelial-to-mesenchymal transition and as therapeutic targets against breast cancers.Experimental biology and medicine (Maywood, N.J.) · 2021Review
- The Nek2 centrosome-mitotic kinase contributes to the mesenchymal state, cell invasion, and migration of triple-negative breast cancer cells.Scientific reports · 2021Article
- Centrosome amplification: a quantifiable cancer cell trait with prognostic value in solid malignancies.Cancer metastasis reviews · 2021Review
- High expression of NEK2 promotes gastric cancer progression via activating AKT signaling.Journal of physiology and biochemistry · 2021Article
- Checking NEKs: Overcoming a Bottleneck in Human Diseases.Molecules (Basel, Switzerland) · 2020Review
- Role of E2Fs and mitotic regulators controlled by E2Fs in the epithelial to mesenchymal transition.Experimental biology and medicine (Maywood, N.J.) · 2019Review
- PCNA and JNK1-Stat3 pathways respectively promotes and inhibits diabetes-associated centrosome amplification by targeting at the ROCK1/14-3-3σ complex in human colon cancer HCT116 cells.Journal of cellular physiology · 2019Article
- Centrosome aberrations and chromosome instability contribute to tumorigenesis and intra-tumor heterogeneity.Journal of cancer metastasis and treatment · 2018Article
- The E2F activators control multiple mitotic regulators and maintain genomic integrity through Sgo1 and BubR1.Oncotarget · 2017Article
- Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Centrosome amplification (CA) is a contributor to carcinogenesis, generating aneuploidy, and chromosome instability. Previous work shows that breast adenocarcinomas have a higher frequency of centrosome defects compared to normal breast tissues. Abnormal centrosome phenotypes are found in pre-malignant lesions, suggesting an early role in breast carcinogenesis. However, the role of CA in breast cancers remains elusive. Identification of pathways and regulatory molecules involved in the generation of CA is essential to understanding its role in breast tumorigenesis. We established a breast cancer model of CA using Her2-positive cells. Our goal was to identify centrosome cycle molecules that are deregulated by aberrant Her2 signaling and the mechanisms driving CA. Our results show some Her2+ breast cancer cell lines harbor both CA and binucleation. Abolishing the expression of Cdk4 abrogated both CA and binucleation in these cells. We also found the source of binucleation in these cells to be defective cytokinesis that is normalized by downregulation of Cdk4. Protein levels of Nek2 diminish upon Cdk4 knockdown and vice versa, suggesting a molecular connection between Cdk4 and Nek2. Knockdown of Nek2 reduces CA and binucleation in this model while its overexpression further enhances centrosome amplification. We conclude that CA is modulated through Cdk4 and Nek2 signaling and that binucleation is a likely source of CA in Her2+ breast cancer cells.
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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.