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Abstract：
Glioblastoma (GBM) is the malignant form of glioma, and the interplay of different pathways working in concert in GBM development and progression needs to be fully understood. Wnt signaling and sonic hedgehog (SHH) signaling pathways, having basic similarities, are among the major pathways aberrantly activated in GBM, and hence, need to be targeted. It becomes imperative, therefore, to explore the functioning of these pathways in context of each other in GBM. An integrative approach may help provide new biological insights, as well as solve the problem of identifying common drug targets for simultaneous targeting of these pathways. The beauty of this approach is that it can recapitulate several known facts, as well as decipher new emerging patterns, identifying those targets that could be missed when relying on one type of data at a time. This approach can be easily extended to other systems to discover key patterns in the functioning of signaling molecules. Studies were designed to assess the relationship between significant differential expression of genes of the Wnt (Wnt/β-catenin canonical and Wnt non-canonical) and SHH signaling pathways and their connectivity patterns in interaction and signaling networks. Further, the aim was to decipher underlying mechanistic patterns that may be involved in a more specific way and to generate a ranked list of genes that can be used as markers or drug targets. These studies predict that Wnt pathway plays a relatively more pro-active role than the SHH pathway in GBM. Further, CTNNB1, CSNK1A1, and Gli2 proteins may act as key drug targets common to these pathways. While CTNNB1 is a widely studied molecule in the context of GBM, the likely roles of CSNK1A1 and Gli2 are found to be relatively novel. It is surmised that Gli2 may be antagonistic to CSNK1A1, preventing the phosphorylation of CTNNB1 and SMO proteins in Wnt and SHH signaling pathway, respectively, by CSNK1A1, and thereby, aberrant activation. New insights into the possible behavior of these pathway molecules relative to each other in GBM reveal some key interesting patterns.
摘要：
胶质母细胞瘤（GBM）是胶质瘤的恶性形式，需要充分理解GBM发展和发展中协调工作的不同途径的相互作用。Wnt信号和声波刺猬（SHH）信号通路，有基本的相似之处，是GBM中异常激活的主要途径之一，因此，必须有针对性。这变得势在必行，因此,探索这些途径在GBM中相互关联的功能。综合方法可能有助于提供新的生物学见解，以及解决了确定同时靶向这些途径的常见药物靶标的问题。这种方法的优点在于它可以概括几个已知的事实，以及破译新出现的模式，识别一次依赖一种类型的数据时可能错过的目标。这种方法可以很容易地扩展到其他系统，以发现信号分子功能中的关键模式。旨在评估Wnt（Wnt/β-catenin规范和Wnt非规范）和SHH信号通路的基因的显着差异表达之间的关系及其在相互作用和信号网络中的连接模式。Further,目的是破译可能以更具体的方式涉及的潜在机制模式，并生成可用作标记或药物靶标的基因排名列表。这些研究预测Wnt途径在GBM中发挥比SHH途径相对更积极的作用。Further,CTNNB1、CSNK1A1和Gli2蛋白可能是这些途径常见的关键药物靶标。虽然CTNNB1是GBM背景下广泛研究的分子，发现CSNK1A1和Gli2的可能作用相对较新。推测Gli2可能拮抗CSNK1A1,阻止CTNNB1和SMO蛋白在Wnt和SHH信号通路中的磷酸化,分别,由CSNK1A1，因此，异常激活。对这些途径分子在GBM中相对于彼此的可能行为的新见解揭示了一些关键的有趣模式。
