Human GSK3β(Glycogen synthase kinase-3 beta) ELISA Kit

Aim: This study aims to identify the prognostic and diagnostic significance of protein kinase-coding genes in pancreatic ductal adenocarcinoma (PDAC), products of which constitute one of the main classes of drug targets in cancer treatment. Material and Methods: Whole-genome gene expression data from seven PDAC cohorts (GSE62452, GSE15471, GSE62165, GSE18670, GSE19280, GSE41368, GSE71989) were included in the integrative transcriptomic analysis (n tumor=252, ncontrol=131). The differentially expressed genes in PDAC compared to controls were identified using random- effects model and were further validated in TCGA (The Cancer Genome Atlas) combined GTEx (Genotype-Tissue Expression) cohort (n tumor=179, ncontrol=171). The prognostic significance of the identified genes was then evaluated by integrating survival and transcriptome data of over 530 (n=530-1302) patients using OSpaad. Results: The integrative transcriptomic analysis revealed a total of seven down-regulated and 33 up-regulated protein kinase-coding genes in PDAC (adjusted p-value <= 0,05, -2 <= z-value <= 2). The validation analysis using TCGA combined GTEx data confirmed 80% (n=32) of the identified differentially expressed genes in PDAC (p<0,01, and fold change >= 2). Amongst, the elevated mRNA expressions of 9 genes (PTK2, TAOK1, CSNK1A1, EIF2AK2, WNK1, CDK12, CDK6, GSK3B, and MAP4K4) were found to be significantly correlated with worse overall survival of patients with PDAC (Logrank p <= 0,05, HR>1). Overexpression of SYK and PRKACB were correlated with better overall survival (Logrank p <= 0,05, HR<1). Discussion: The results of this study suggest that mRNA expression of the identified eleven protein kinase-coding genes can be used as both prognostic and diagnostic biomarkers for further clinical validation.

The ability of cells to migrate and form metastases is one of the fatal hallmarks of cancer that can be conquered only with better understanding of the molecules and regulatory mechanisms involved. The oncogenic PIM kinases have been shown to support cancer cell survival and motility, but the PIM-regulated pathways stimulating cell migration and invasion are less well characterized than those affecting cell survival. Here we have identified the glycogen synthase kinase 3 beta (GSK3B) and the forkhead box P3 (FOXP3) transcription factor as direct PIM targets, whose tumour-suppressive effects in prostate cancer cells are inhibited by PIM-induced phosphorylation, resulting in increased cell migration. Targeting GSK3B is also essential for the observed PIM-enhanced expression of the prostaglandin-endoperoxide synthase 2 (PTGS2), which is an important regulator of both cell migration and adhesion. Accordingly, selective inhibition of PIM activity not only reduces cell migration, but also affects integrin-mediated cell adhesion. Taken together, these data provide novel mechanistic insights on how and why patients with metastatic prostate cancer may benefit from therapies targeting PIM kinases, and how such approaches may also be applicable to inflammatory conditions. (C) 2016 Elsevier Inc. All rights reserved.