A Compendium of Co-regulated Protein Complexes in Breast Cancer Reveals Collateral Loss Events.
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Embargo End Date
ICR Authors
Authors
Ryan, CJ
Kennedy, S
Bajrami, I
Matallanas, D
Lord, CJ
Kennedy, S
Bajrami, I
Matallanas, D
Lord, CJ
Document Type
Journal Article
Date
2017-10-25
Date Accepted
2017-09-18
Abstract
Protein complexes are responsible for the bulk of activities within the cell, but how their behavior and abundance 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 285 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 overexpressed in specific breast cancer subtypes. We found that mutation or deletion of one subunit of a co-regulated complex was often associated with a collateral reduction in protein expression of additional complex members. This collateral loss phenomenon was typically 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.
Citation
Cell systems, 2017, 5 (4), pp. 399 - 409.e5
Source Title
Publisher
CELL PRESS
ISSN
2405-4712
eISSN
2405-4720
Collections
Research Team
Gene Function