Kindlin-1 Links Integrins and Maintenance of Nuclear Shape in Cutaneous Squamous Carcinoma Cells

Kindlins are essential for integrin activation and mechanoresponses. In the epidermis, inherited loss-of-function of the FERMT1 gene, which encodes Kindlin-1, increases the risk of developing cutaneous squamous cell carcinoma (cSCC). Notably, the role of Kindlin-1 in epidermal tumours has remained virtually unexplored. In this study, we analyzed the consequences of FERMT1 inactivation in a cSCC cell model. Kindlin-1-depleted cells exhibited decreased number and size of focal adhesions, as well as alterations in actin stress fibres and the F-actin perinuclear cap. Significantly, FERMT1 inactivation also resulted in reduced nuclear volume and total surface area. These abnormalities were not ameliorated by exogenous expression of Kindlin-2 or a Kindlin-1 mutant incapable of binding to integrins. In contrast, nuclear dimensions in Kindlin-1-deficient cells were restored in the presence of a constitutively active RhoA protein. These findings are consistent with the concept that Kindlin-1 plays an essential role mediating integrin signalling and RhoA activation to modulate perinuclear actin filaments and nuclear morphology.