In mitosis integrins reduce adhesion to extracellular matrix and strengthen adhesion to adjacent cells.

To enter mitosis, most adherent animal cells reduce adhesion, which is followed by cell rounding. How mitotic cells regulate adhesion to neighboring cells and extracellular matrix (ECM) proteins is poorly understood. Here we report that, similar to interphase, mitotic cells can employ integrins to initiate adhesion to the ECM in a kindlin- and talin-dependent manner. However, unlike interphase cells, we find that mitotic cells cannot engage newly bound integrins to actomyosin via talin or vinculin to reinforce adhesion. We show that the missing actin connection of newly bound integrins leads to transient ECM-binding and prevents cell spreading during mitosis. Furthermore, β1 integrins strengthen the adhesion of mitotic cells to adjacent cells, which is supported by vinculin, kindlin, and talin1. We conclude that this dual role of integrins in mitosis weakens the cell-ECM adhesion and strengthens the cell-cell adhesion to prevent delamination of the rounding and dividing cell.