Kindlin-1 Links Integrins and Maintenance of Nuclear Shape in Cutaneous Squamous Carcinoma Cells
- 1Department of Physiology and Pharmacology, Western University, London, ON N6A 5C1, Canada
- 2Children’s Health Research Institute, London, ON N6A 5C1, Canada
- 3Department of Oncology, Western University, London, ON N6A 5C1, Canada
Abstract
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.
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BibTeX
@article{varela2026kindlin1,
title = {{Kindlin-1 Links Integrins and Maintenance of Nuclear Shape in Cutaneous Squamous Carcinoma Cells}},
author = {Alejandra Varela and Samar Sayedyahossein and Rithwik Ramachandran and Lina Dagnino},
journal = {Cells},
year = {2026},
month = oct,
doi = {10.3390/cells15211991},
url = {https://www.mdpi.com/2073-4409/15/21/1991},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Kindlin-1 Links Integrins and Maintenance of Nuclear Shape in Cutaneous Squamous Carcinoma Cells
AU - Alejandra Varela
AU - Samar Sayedyahossein
AU - Rithwik Ramachandran
AU - Lina Dagnino
PY - 2026
DA - 2026/10/31
JO - Cells
DO - 10.3390/cells15211991
UR - https://www.mdpi.com/2073-4409/15/21/1991
AB - 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.
SN - 2073-4409
ER -