biostudies-literatureTran ATGouvernement du Canada | Natural Sciences and Engineering Research Council of Canadathe Bird Dogs Chair in Translational Oncology at the University of AlbertaEuropean Research CouncilFonds de Recherche du Québec - SantéNational Institute of HealthNIH: National Institute of HealthNCI NIH HHSNIGMS NIH HHS1476-1488https://www.ebi.ac.uk/biostudies/studies/S-EPMC12404997biostudies-literatureUnknown24(9)Cell migration in mechanically confined environments is a crucial step of metastatic cancer progression. Nonetheless, the molecular components and processes mediating such behaviour are still not fully understood. Here we demonstrate that a pool of the scaffolding protein anillin and its cofactor Ect2, which are both predominantly nuclear proteins and critical mediators of cytokinesis, is present in the cytoplasm of multiple interphase cell types that promote confined cell migration. Confined migration in biomimetic microfluidic models triggers the actomyosin-binding-dependent recruitment of anillin to the plasma membrane at the poles of migrating cells in a manner that scales with microenvironmental stiffness and confinement. The guanine nucleotide exchange activity of Ect2 is required foNature materialsCytoplasmic anillin and Ect2 promote RhoA/myosin II-dependent confined migration and invasion.PMC12404997R35 GM147101R35 GM156305R01 GM142175R01 CA254193U54 CA261694R01 CA257647Amitrano AFriedl PGerecht SZuo YLewis JDAfthinos AParlani MAgarwal BTuntithavornwat SGu LBera KStoletov KNath SMartin SSKalab PLee SJWu PHWisniewski EOKiepas AIfemembi BJamieson JJKonstantopoulos KTran ATZhang YHabib DMistriotis PfalseCytoplasmic anillin and Ect2 promote RhoA/myosin II-dependent confined migration and invasion.Cell migration in mechanically confined environments is a crucial step of metastatic cancer progression. Nonetheless, the molecular components and processes mediating such behaviour are still not fully understood. Here we demonstrate that a pool of the scaffolding protein anillin and its cofactor Ect2, which are both predominantly nuclear proteins and critical mediators of cytokinesis, is present in the cytoplasm of multiple interphase cell types that promote confined cell migration. Confined migration in biomimetic microfluidic models triggers the actomyosin-binding-dependent recruitment of anillin to the plasma membrane at the poles of migrating cells in a manner that scales with microenvironmental stiffness and confinement. The guanine nucleotide exchange activity of Ect2 is required fo2025-01-01T00:00:00Z2025 Sep2026-05-29T21:20:57.269Z2026-04-08T06:01:44.691ZS-EPMC124049974057173410.1038/s41563-025-02269-9