@article{4126,
  keywords = {Animals, Mice, Extracellular Matrix, Signal Transduction, Female, Epithelial Cells, Septins, Breast Neoplasms, Tumor Microenvironment, Epithelial-Mesenchymal Transition, Cell Culture Techniques, Focal Adhesions, Transforming Growth Factor beta, Snail Family Transcription Factors, Mammary Glands, Animal, Integrin beta1, Protein Serine-Threonine Kinases, Kinesins, Acrylic Resins},
  author = {Emann Rabie and Sherry Zhang and Connor Dunn and Celeste Nelson},
  title = {Substratum stiffness signals through integrin-linked kinase and β1-integrin to regulate midbody proteins and abscission during EMT.},
  abstract = { <p>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.</p> },
  year = {2021},
  journal = {Mol Biol Cell},
  volume = {32},
  pages = {1664-1676},
  month = {2021 Aug 19},
  issn = {1939-4586},
  doi = {10.1091/mbc.E21-02-0072},
  language = {eng},
}