Kindlins: Roles in development and cancer progression

Abstract

The Kindlins are FERM domain proteins comprising three members (Kindlin-1, -2 and -3) which are evolutionarily conserved. Kindlins bind with β-integrin cytoplasmic tails and execute broad biological functions including directed cell migration, proliferation, differentiation and survival. In light of more and more evidence point to the importance of Kindlin family members in normal development and human diseases especially in cancers, we aim to portrait the profile of Kindlins in the regulation of embryonic development and cancer progression. We first summarize all the known binding proteins for individual member of Kindlin family. We then outline the Kindlin-regulated signaling pathways including Wnt/β-catenin, TGFβ, EGFR, and Hedgehog signalings. Furthermore, we descript the pivotal role of Kindlins in embryonic development in detail with notions that Kindlin-1 is highly expressed in endo/ectodermal originated tissues, Kindlin-2 is highly expressed in mesoderm-derived tissues and Kindlin-3 is highly expressed in mesoderm- and ectoderm-derived tissues. Deregulation of Kindlins is generally reported in cancers from different organs. We also briefly descript the role of Kindlins in other diseases. Finally, we update the recent understanding of how Kindlins are regulated and modified as well as the degradation mechanism of Kindlins, respectively.

Keywords: Cancer; Development; FREMT gene; Kindlin; Scaffold protein.