ArticleMolecular biology of the cell2021
Substratum stiffness signals through integrin-linked kinase and β1-integrin to regulate midbody proteins and abscission during EMT.
Article in Molecular biology of the cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 27 citations in OpenAlex.
- Septin crosstalk with microtubules and actin is regulated by a GSK3-dependent phosphoswitch.bioRxiv : the preprint server for biology · 2026Article
- Single-cell and spatial transcriptomic characterization of pulmonary pleomorphic carcinoma.Communications biology · 2025Article
- The Dystrophin-Dystroglycan complex ensures cytokinesis efficiency in Drosophila epithelia.EMBO reports · 2025Article
- Integrin β1 in breast cancer: mechanisms of progression and therapy.Breast cancer (Tokyo, Japan) · 2025Review
- Review
- Germ fate determinants protect germ precursor cell division by reducing septin and anillin levels at the cell division plane.Molecular biology of the cell · 2024Article
- Integrating integrins with the hallmarks of cancer.Matrix biology : journal of the International Society for Matrix Biology · 2024Review
- ITGB1 and DDR activation as novel mediators in acquired resistance to osimertinib and MEK inhibitors in EGFR-mutant NSCLC.Scientific reports · 2024Article
- An oncogenic isoform of septin 9 promotes the formation of juxtanuclear invadopodia by reducing nuclear deformability.Cell reports · 2023Article
- α-catenin mechanosensitivity as a route to cytokinesis failure through sequestration of LZTS2.bioRxiv : the preprint server for biology · 2023Article
- The role of matrix stiffness in breast cancer progression: a review.Frontiers in oncology · 2023Review
- Septins as membrane influencers: direct play or in association with other cytoskeleton partners.Frontiers in cell and developmental biology · 2023Review
- New Perspectives on the Role of Integrin-Linked Kinase (ILK) Signaling in Cancer Metastasis.Cancers · 2022Article
- Mechanics and regulation of cytokinetic abscission.Frontiers in cell and developmental biology · 2022Review
- Computational Drug Repurposing Approach to Identify Novel Inhibitors of ILK Protein for Treatment of Esophageal Squamous Cell Carcinoma.Journal of oncology · 2022Article
- Meeting report - the ever-fascinating world of septins.Journal of cell science · 2021Article
- Cep55: abscission boss or assistant?Trends in cell biology · 2021Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Abscission is the final stage of cytokinesis during which the parent cell physically separates to yield two identical daughters. Failure of abscission results in multinucleation (MNC), a sign of genomic instability and a precursor to aneuploidy, enabling characteristics of neoplastic progression. Induction of epithelial-mesenchymal transition (EMT) causes MNC in mammary epithelial cells cultured on stiff microenvironments that have mechanical properties similar to those found in breast tumors, but not on soft microenvironments reminiscent of the normal mammary gland. Here we report that on stiff microenvironments, EMT signaling through Snail up-regulates the midbody-associated proteins septin-6, Mklp1, and anillin, leading to abscission failure and MNC. To uncover the mechanism by which stiff microenvironments promote MNC in cells undergoing EMT, we investigated the role of cell-matrix adhesion through β1-integrin and integrin-linked kinase (ILK). We found that ILK expression, but not kinase activity, is required for EMT-associated MNC in cells on stiff microenvironments. Conversely, increasing focal adhesions by expressing an autoclustering mutant of β1-integrin promotes MNC in cells on soft microenvironments. Our data suggest that signaling through focal adhesions causes failure of cytokinesis in cells actively undergoing EMT. These results highlight the importance of tissue mechanics and adhesion in regulating the cellular response to EMT inducers.
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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.