Abstract IA12: Widespread rewiring of genetic interaction networks upon cancer pathway activation

Genetic interactions can reconstruct the wiring diagram of biological processes in health and disease. Gene-gene interactions are identified by simultaneously perturbing multiple gene products and identifying instances when the expected and experimentally measured phenotypes differ, e.g. aggravating or buffering phenotypic outcomes. Systematic gene-gene depletion experiment have been used to build comprehensive maps of cellular processes in unicellular and multicellular organisms, to place novel components into the context of known pathways and delineate epistatic relationships between components.Cellular signaling networks coordinate physiological processes in all multicellular organisms. Within signaling networks, the interplay of different modules controls signaling activity dependent onto the cellular context. We here generated a context-dependent genetic interaction network of a Wnt signaling pathway, which has been implicated in many developmental and oncogenic processes. To assess changes in genetic network architecture, we measured >290,000 double perturbations in a baseline state, after activation by Wnt ligands or loss of the tumor suppressor APC. We found that genetic interactions within the Wnt network globally rewired after pathway activation. Distinct groups of responsive functional relations were identified in the between-state or state-specific networks. State-dependent and between-state genetic interaction maps identified responsive functional modules in n...
Source: Molecular Cancer Therapeutics - Category: Cancer & Oncology Authors: Tags: Model Organisms to Identify Synthetic Lethal Interactions: Oral Presentations - Invited Abstracts Source Type: research