Investigation of linear paths in human wnt signaling network

Abstract

Recently, the evolutionarily conserved signaling pathways which are involved in embryonic development are on the march for many research since the deregulations seen in the mechanism of these patways results in several diseases, especially in cancer. Hence interaction networks have begun to be aooreciated because it may be useful to understand the general principles of biological systems by means of systems biology. This study is concered with the Wnt signaling pathway that are known as Wnt-beta-catenin, planar cell polarity (PCP) and Wnt-calcium (Wnt/Ca2+) pathways and presents potensial targeting points for cancer drug progression. Here, the reconstruction of Wnt signaling network was performed for Homo Sapiens via integration of interactome data and Gene Ontology annotations since the whole Wnt mechanism is not well understood in human due to limited experimental findings. In addition to be Wnt sub-networks, the whole Wnt signaling network was also investigation to see the globeal pictuer. All the reconstructed networks showed scale-free topologies. Moreover, the linear paths in which the signal is transferred from ligands (input) to transcription factor (output) were identified. the graph theoretical analysis was performed for analyzing the toplogical properties of the network proteins. Then, the crosstalk analysis was applied in order to detect yhe significant bridging proteins in all sub-networks. Finally, the size reduction of the network was done; however, it caused a significant loss in core proteins, and did not result in a small network for convenient usage. The proteins Beta-catenin, LEF1, GSK3b, APC, AXIN and DKK1, which are reported to be potential drug targetss in literature, are found as the essential proteins of the Wnt network. Besides, LEF1, WNT7A and FZD9 proteins which are the participants with the highest percentages in the linear path analysis and CNKD3, TGFR2 and MYC which are the specific proteins in linear paths are also proposed as potential drug targets.