Regulation of protein complex partners as a compensatory mechanism in aneuploid tumors
- European Institute of Oncology, Italy
Abstract
Aneuploidy, a state of chromosome imbalance, is a hallmark of human tumors, but its role in cancer still remains to be fully elucidated. To understand the consequences of whole-chromosome-level aneuploidies on the proteome, we integrated aneuploidy, transcriptomic and proteomic data from hundreds of TCGA/CPTAC tumor samples. We found a surprisingly large number of expression changes happened on other, non-aneuploid chromosomes. Moreover, we identified an association between those changes and co-complex members of proteins from aneuploid chromosomes. This co-abundance association is tightly regulated for aggregation-prone aneuploid proteins and those involved in a smaller number of complexes. On the other hand, we observe that complexes of the cellular core machinery are under functional selection to maintain their stoichiometric balance in aneuploid tumors. Ultimately, we provide evidence that those compensatory and functional maintenance mechanisms are established through post-translational control and that the degree of success of a tumor to deal with aneuploidy-induced stoichiometric imbalance impacts the activation of cellular protein degradation programs and patient survival.
Data availability
The code performing all analyses in this study is available at https://github.com/SengerG/Coregulation-of-complexes-in-Aneuploidtumors.git
Article and author information
Author details
Stefano Santaguida
Funding
Fondazione AIRC (MFAG 21791)
- Martin H Schaefer
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2022, Senger et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Regulation of protein complex partners as a compensatory mechanism in aneuploid tumors
eLife 11:e75526.
https://doi.org/10.7554/eLife.75526
