Rabbit Anti-Human URP2 (a.a. 401-500) Polyclonal antibody

Neutrophilic granulocytes constitute the body's first line of defence against bacterial and fungal pathogens and orchestrate the inflammatory response. The analysis of monogenic defects of neutrophilic granulocytes has yielded important insights into mechanisms of the innate immune system. Severe congenital neutropenia is defined by decreased numbers of absolute neutrophil counts and may be caused by mutations in ELANE/ELA2, HAX1, GFI1, WASP or G6PC3. Qualitative defects of neutrophilic granulocytes affect migration, activation and bacterial killing capacity which are manifested clinically as leukocyte adhesion deficiencies I-III (ITGB2, SLC35C1, FERMT3) and chronic granulomatous disease (CYBB, NCF1, NCF2, CYBA).

FERMT3, also known as kindlin-3, is one of three kindlin family members expressed in mammals. Kindlins are cytosolic, adaptor proteins that are important activators and regulators of integrin function. They have also been shown to play critical roles in the development and progression of various cancers. In the present study, we hypothesized that FERMT3 would enhance glioblastoma multiforme (GBM) cell survival. Indeed, expression level analyses showed significant FERMT3 upregulation in human glioma tissues, as compared to normal brain tissues. The effect was particularly pronounced in high-grade gliomas. We then demonstrated that FERMT3 knockdown suppresses glioma cell proliferation and chemoresistance to temozolomide (TMZ). To determine the mechanism by which FERMT3 enhances glioma cell proliferation and chemoresistance, we examined the effects of FERMT3 on integrin activation and Wntip-catenin signaling. Through the use of western blot assays and TOPflash and FOPflash plasmid transfection into glioma cells lines, we demonstrated that FERMT3 regulates glioma cell activity through integrin-mediated Wnt/beta-catenin signaling. These results suggest that FERMT3 activates integrin activity in high-grade gliomas to enhance glioma cell survival and chemoresistance. The present study thus indicates a potential role for FERMT3 as a genetic target in the treatment of GBM. (C) 2017 Elsevier B.V. All rights reserved.