ArticleOncogene2011
A critical role of integrin-linked kinase, ch-TOG and TACC3 in centrosome clustering in cancer cells.
Article in Oncogene, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 92 citations in OpenAlex.
- The PLK4 inhibitor RP-1664 demonstrates potent efficacy in neuroblastoma preclinical models through a dual mechanism of sensitivity.Nature communications · 2026Article
- Meiotic progression in multinuclear mouse spermatocytes without the spindle pole clustering motor protein KIFC1 or cytokinesis forms single-cell late-stage spermatids.Scientific reports · 2025Article
- Structural characterization and inhibition of the interaction between ch-TOG and TACC3.The Journal of cell biology · 2025Article
- TACC3 enhances glycolysis in bladder cancer cells through inducing acetylation of c-Myc.Cell death & disease · 2025Article
- Development and validation of a radiomic prediction model for TACC3 expression and prognosis in non-small cell lung cancer using contrast-enhanced CT imaging.Translational oncology · 2025Article
- Article
- Cortical dynein drives centrosome clustering in cells with centrosome amplification.Molecular biology of the cell · 2023Article
- Therapeutic gene silencing ofScience advances · 2023Article
- Whole-Genome Duplication and Genome Instability in Cancer Cells: Double the Trouble.International journal of molecular sciences · 2023Review
- The kinase activity of integrin-linked kinase regulates cellular senescence in gastric cancer.Cell death & disease · 2022Article
- Centrosome Defects in Hematological Malignancies: Molecular Mechanisms and Therapeutic Insights.Blood science (Baltimore, Md.) · 2022Review
- Integrin-linked kinase (ILK): the known vs. the unknown and perspectives.Cellular and molecular life sciences : CMLS · 2022Review
- Keep Calm and Carry on with Extra Centrosomes.Cancers · 2022Review
- Characterization of a recently synthesized microtubule-targeting compound that disrupts mitotic spindle poles in human cells.Scientific reports · 2021Article
- Integrin-Linked-Kinase Overexpression Is Implicated in Mechanisms of Genomic Instability in Human Colorectal Cancer.Digestive diseases and sciences · 2021Article
- A Potential Role for Integrin-Linked Kinase in Colorectal Cancer Growth and Progression via Regulating Senescence and Immunity.Frontiers in genetics · 2021Review
- Integrin-linked kinase (ILK) regulates KRAS, IPP complex and Ras suppressor-1 (RSU1) promoting lung adenocarcinoma progression and poor survival.Journal of molecular histology · 2020Article
- TRIGGERING ANAPHASE CATASTROPHE TO COMBAT ANEUPLOID CANCERS.Transactions of the American Clinical and Climatological Association · 2020Article
- Targeting centrosome amplification, an Achilles' heel of cancer.Biochemical Society transactions · 2019Review
- Inhibition of CPAP-tubulin interaction prevents proliferation of centrosome-amplified cancer cells.The EMBO journal · 2019Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Many cancer cells contain more than two centrosomes, which imposes a potential for multipolar mitoses, leading to cell death. To circumvent this, cancer cells develop mechanisms to cluster supernumerary centrosomes to form bipolar spindles, enabling successful mitosis. Disruption of centrosome clustering thus provides a selective means of killing supernumerary centrosome-harboring cancer cells. Although the mechanisms of centrosome clustering are poorly understood, recent genetic analyses have identified requirements for both actin and tubulin regulating proteins. In this study, we demonstrate that the integrin-linked kinase (ILK), a protein critically involved in actin and mitotic microtubule organization, is required for centrosome clustering. Inhibition of ILK expression or activity inhibits centrosome clustering in several breast and prostate cancer cell lines that have centrosome amplification. Furthermore, cancer cells with supernumerary centrosomes are significantly more sensitive to ILK inhibition than cells with two centrosomes, demonstrating that inhibiting ILK offers a selective means of targeting cancer cells. Live cell analysis shows ILK perturbation leads cancer cells to undergo multipolar anaphases, mitotic arrest and cell death in mitosis. We also show that ILK performs its centrosome clustering activity in a focal adhesion-independent, but centrosome-dependent, manner through the microtubule regulating proteins TACC3 and ch-TOG. In addition, we identify a specific TACC3 phosphorylation site that is required for centrosome clustering and demonstrate that ILK regulates this phosphorylation in an Aurora-A-dependent manner.
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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.