Reconstruction of Different Modes of WNT Dependent Protein Networks from Time Series Protein Quantification.

ABSTRACT

Protein signaling networks are crucial cornerstones in cellular responses. Deregulation causes various diseases, including cancer. One pathway that is frequently deregulated in cancer is the WNT signaling pathway. It has been shown that WNT signaling is highly context-dependent and the availability of receptors and ligands determines downstream signaling. In order to reveal which signaling pathways are activated by a specific receptor-ligand combination, we overexpressed the non-canonical WNT receptor ROR2 in the human breast cancer cell line MCF-7 and stimulated it with its putative ligand WNT11. Based on characterization of the cells by Reverse Phase Protein Array (RPPA), we integrated the proteomic data by network reconstruction analysis with prior knowledge from a pathway database. Using this approach, we were able to identify novel edges that differed upon ROR2 overexpression and WNT11 stimulation.