A compendium of co-regulated protein complexes in breast cancer reveals collateral loss events

Abstract

Protein complexes are responsible for the bulk of activities within the cell, but how their behavior and composition varies across tumors remains poorly understood. By combining proteomic profiles of breast tumors with a large-scale protein-protein interaction network, we have identified a set of 258 high-confidence protein complexes whose subunits have highly correlated protein abundance across tumor samples. We used this set to identify complexes that are reproducibly under- or over-expressed in specific breast cancer subtypes. We found that mutation or deletion of one subunit of a complex was often associated with a collateral reduction in protein expression of additional complex members. This collateral loss phenomenon was evident from proteomic, but not transcriptomic, profiles suggesting post-transcriptional control. Mutation of the tumor suppressor E-cadherin (CDH1) was associated with a collateral loss of members of the adherens junction complex, an effect we validated using an engineered model of E-cadherin loss.