Kindlin-1

Kindlin-1 is a protein and a component of focal adhesion in epithelial cells. Kindlin-1 is encoded by the FERMT1 gene (FERMT1 stands for: FERM Domain Containing Kindlin 1) which is localized on chromosome 20p12.3.

Kindlin-1 is a member of the fermitin family. Kindlin-1 contains a FERM domain and a pleckstrin homology domain. Kindlin-1 is involved in integrin signaling and in linking the actin cytoskeleton to the extracellular matrix. Mutations in this gene are associated with Kindler syndrome.

Kindlin-1 is involved in cell adhesion of epithelial cells. It contributes to integrin activation. When co-expressed with talin, it enhances the activation of ITGA2B. Kindlin-1 is required for normal proliferation of keratinocytes and also for normal polarization of basal keratinocytes in the skin and for normal cell shape. Kindlin-1 plays a major role in the adhesion of keratinocytes to fibronectin and laminin and in the normal migration of keratinocytes to wounds. May mediate TGF-beta 1 signaling during tumor progression.

In most cases of Kindler syndrome, Kindlin-1 is reduced or absent in keratinocytes, leading to impaired integrin activation, cell adhesion and migration. It has been shown that skin and keratinocytes of patients with Kindler syndrome have a significantly reduced expression of EGFR, leading to impaired EGF-dependent signaling and cell migration. Furthermore, kindlin-1 protects the EGFR from lysosomal-mediated degradation (Michael M et al. 2019).

In breast cancer, increased expression of the cytoskeletal adaptor protein Kindlin-1 was associated with an increased risk of lung metastasis. Loss of kindlin-1 reduced α4-integrin-mediated adhesion of mammary tumor cells to the adhesion molecule VCAM-1 on endothelial cells. This apparently contributes functionally to early pulmonary metastasis of breast cancer (Bonin F et al. 2022).

1. Azorin P et al. (2018) Distinct expression profiles and functions of Kindlins in breast cancer. J Exp Clin Cancer Res 37:281.
2. Bonin F et al. (2022) Kindlin-1 drives early steps of breast cancer metastasis. Cancer Commun (Lond) 42:1036-1040.
3. Michael M et al. (2019) Kindlin-1 Regulates Epidermal Growth Factor Receptor Signaling. J Invest Dermatol 139:369-379.
4. Zhang G et al. (2016) Kindlin-1 Regulates Keratinocyte Electrotaxis. J Invest Dermatol 136:2229-2239.