A Compendium of Co-regulated Protein Complexes in Breast Cancer Reveals Collateral Loss Events.
View/ Open
Date
2017-10-25ICR Author
Author
Ryan, CJ
Kennedy, S
Bajrami, I
Matallanas, D
Lord, CJ
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Cell Line, Tumor
Humans
Breast Neoplasms
Cadherins
Proteome
Proteomics
Gene Expression Regulation, Neoplastic
RNA Processing, Post-Transcriptional
Mutation
Genes, Tumor Suppressor
Female
Protein Interaction Maps
MCF-7 Cells
Research team
Gene Function
Language
eng
Date accepted
2017-09-18
License start date
2017-10-11
Citation
Cell systems, 2017, 5 (4), pp. 399 - 409.e5
Publisher
CELL PRESS