DISCOVERIES (ISSN 2359-7232), 2016, April-June issue

CITATION: 

Submitted: June 10, 2016; Revised: June 29, 2016; Accepted: June 29, 2016; Published: June 30, 2016;

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Of Kindlins and Cancer

Edward F. Plow*, Mitali Das, Katarzyna Bialkowska, Khalid Sossey-Alaoui*

Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA

*Correspondence to: Edward F. Plow, PhD and Khalid Sossey-Alaoui, PhD, Department of Molecular Cardiology/NB5-50, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195, Phone: 1-216-445-8200; Emails: plowe@ccf.org and sosseyk@ccf.org 

Abstract

Kindlins are 4.1-ezrin-ridixin-moesin (FERM) domain containing proteins. There are three kindlins in mammals, which share high sequence identity.  Kindlin-1 is expressed primarily in epithelial cells, kindlin-2 is widely distributed and is particularly abundant  in adherent cells, and kindlin-3 is expressed primarily in hematopoietic cells. These distributions are not exclusive; some cells express multiple kindlins, and transformed cells often exhibit aberrant expression, both in the isoforms and the levels of kindlins. Great interest in the kindlins has emerged from the recognition from that they play major roles in controlling integrin function.  In vitro studies, in vivo studies of mice deficient in kindlins, and studies of patients with genetic deficiencies of kindlins have clearly established that they regulate the capacity of integrins to mediate their functions. Kindlins are adaptor proteins; their function emanate from their interaction with binding partners, including the cytoplasmic tails of integrins and components of the actin cytoskeleton. The purpose of this review is to provide a brief overview of kindlin structure and function, a consideration of their binding partners, and then to focus on the relationship of each kindlin family member with cancer. In view of many correlations of kindlin expression levels and neoplasia and the known association of integrins with tumor progression and metastasis, we consider whether regulation of kindlins or their function would be attractive targets for treatment of cancer. 

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