This study points out that Gli2 upregulation could be corBTTAA biological activity related with GBM progression. Since Gli2 degradation happens by means of GSK3-dependent phosphorylation and ubiquitination, escalating the activity of GSK3 can be oneCanCer InformatICs 2014:potential mechanism of therapy. What is more conclusive is the fact that, GSK3 is identified upregulated in typical tissues and not in tumors, therefore Gli2 is just not degraded in tumors, and so, might play a pro-active role in GBM tumor development.CSNK1A1 and Gli2: antagonistic proteins and drug targets in glioblastomafigure 1. (Continued)figure 1. PPI networks overlaid with gene expression information. (A) PPI networks had been overlaid with gene expression data for every gene in tumors. (B) PPI networks had been overlaid with gene expression information for every gene in standard tissues. Considerably differentially expressed nodes are colored based on expression values. (C) Nodes in PPI network sized and colored in line with node degree distribution, larger size of a node corresponds to greater node degree, when the colour gradient from green to yellow to red denotes reduce to larger node degrees.A further molecule that seems to connect the two pathways is CSNK1A1 (Fig. 2B), and is in concentrate due to its significant differential expression and higher node degree in PPI network overlaid with gene expression data from tumors (Fig. 1a and c). It’s connected to each Gli2 and CTNNB1 in pathway network. CSNK1A1 phosphorylates CTNNB1 in Wnt pathway and SMO in SHH pathway, thereby inactivating these proteins. The mechanism by which CTNNB1 and SMOproteins are prevented from inactivation or remain activated within the presence of high levels of CSNK1A1 in GBM tumors is actually a matter of additional experimental investigation. Even so, the emerging patterns within this study point to a achievable antagonistic part of Gli2 within this mechanism as is explained in “Insights from key emerging patterns” section. The gene or protein expression levels of CTNNB1, CSNK1A1, and Gli2 happen to be reported as PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/21338877 prognostic andCanCer InformatICs 2014:Mishra(Continued)CanCer InformatICs 2014:CSNK1A1 and Gli2: antagonistic proteins and drug targets in glioblastomafigure 2. (Continued)figure 2. Pathway network involving the Wnt- and SHH pathway molecules. Gli2 appears as the connector molecule of Wnt- and SHH pathway in this network, connected to CSNK1A1 and other individuals in Wnt pathway network, and SMO and others in SHH pathway network. Yellow-colored nodes are the initial neighbors (directly connected) of (a) Gli2, (b) CSNK1A1, and (c) CTNNB1.predictor aspects in quite a few kinds of tumors. CTNNB1 and Gli1 are identified to serve as prognostic markers in GBM. 23 Significant correlation was observed in between high -catenin (CTNNB1) activity and poor prognosis of the sufferers, and this was thought of as “a sturdy and independent prognostic issue in breast cancer.”24 CTNNB1 has also been located to serve as a beneficial prognostic marker in non-small cell lung cancer and gastric cancer25,26 and in 
pair with CSNK1E, a prognostic marker in colorectal cancer.27 CSNK1A1 has been reported to be overexpressed at each mRNA and protein levels in melanoma cells as compared to regular cells top for the proposition that it might serve as a valuable diagnostic marker. 28 Higher Gli2 protein expression level in hepatocellular carcinoma (HCC) was found to become related with poor prognosis in HCC patients immediately after hepatectomy29 and inside the case of intrahepatic cholangiocellular carcinoma (ICC) was found to become linked with unfavorable overall surviv.
