Magnified image of the boxed region are shown to demonstrate co-localization

Magnified image of the boxed region are shown to demonstrate co-localization. integrin. Silencing of 6 integrin expression however, had no significant effect on the kactual of 3 integrin or its distribution in early endosomes. These results indicate that 3 and 6 integrins have significantly different internalization kinetics and that coordination exists between them for internalization. This article is protected by copyright. All rights reserved strong AM 2201 class=”kwd-title” Keywords: integrin, laminin, internalization kinetics, endosomes, prostate cancer Integrins are cell surface receptors involved in cell matrix adhesion, signaling, and cell migration [Hood and Cheresh, 2002; Sroka et al., 2010; Watt, 2002]. The laminin binding integrins (3 and 6 containing heterodimers; 31, 61, and 64) represent a conserved class of integrins essential for the normal development of vertebrate and non-vertebrate life forms [Frank and Miranti, 2013; Hynes, 2002; Longmate and Dipersio, 2014; Marchetti et al., 2013]. For simplicity, 61 and 64 integrins will be referred to here as 6 integrin. Integrins 3 and 6 function coordinately during embryonic development [De Arcangelis et al., 1999; DiPersio et AM 2201 al., 1997] as well as in adult processes such as epithelial regeneration and wound healing [Longmate and Dipersio, 2014; Margadant et al., 2009]. Mice lacking the 6 integrin AM 2201 die shortly after birth because of severe blistering of the skin and other epithelia [Georges-Labouesse et al., 1996], a defect that can only be partially compensated by 3 integrin [De Arcangelis et al., 1999; van der Neut et al., 1996]. During development and wound healing, both of these integrins show an orchestrated redistribution of their cellular localization that affects their function [Shimizu et al., 2012]. During cell migration, 3 integrin [Barczyk et al., 2010] is observed at the tip of the lamellipodia and is involved in the deposition of a provisional extracellular matrix, subsequently utilized by 6 integrin for collective epithelial migration [Margadant et al., 2009]. In humans, 3 and 6 integrins are expressed in various epithelial cancers [Desgrosellier and Cheresh, 2010; Stipp, 2010]. Only laminin binding integrins are detected in biopsy and prostatectomy specimens of primary prostate tumors, as well as in bone metastasis specimens [Schmelz et al., 2002], demonstrating a loss of the variety of integrin expression in prostate cancer as compared to normal glands [Cress et al., 1995]. Although the majority of prostate cancers (80%) express either/both 3 or 6 integrins on the tumor cell surface, 26% express only integrin 6 [Schmelz et al., 2002]. Additionally, the loss of surface 3 integrin expression positively correlated with high Gleason grade and the pathological stage of the cancer [Schmelz et al., 2002]. Likewise, expression of 6 integrin is an important determinant of tumor progression, reduced patient survival, and increased metastasis [Ports et al., 2009; Schmelz et al., 2002]. Integrin 6 is a marker of prostate cancer stem cells or tumor initiating cells [Park et al., 2016; Schmelz et al., 2005]. Previous work has AM 2201 shown a strong expression of 6 integrin during perineural invasion [Sroka et al., 2010] Rabbit polyclonal to ABHD14B and bone metastasis in prostate cancer [Landowski et al., 2014; Schmelz et al., 2002]. A tumor-specific functional variant, 6p, is a key contributor to cancer metastasis [Demetriou and Cress, 2004; Demetriou et.

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