1. Cancer Biology
  2. Computational and Systems Biology

Regulation of protein complex partners as a compensatory mechanism in aneuploid tumors

  1. Gökçe Senger
  2. Stefano Santaguida
  3. Martin H Schaefer  Is a corresponding author
  1. European Institute of Oncology, Italy
https://doi.org/10.7554/eLife.75526
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  1. Gökçe Senger
  2. Stefano Santaguida
  3. Martin H Schaefer
(2022)
Regulation of protein complex partners as a compensatory mechanism in aneuploid tumors
eLife 11:e75526.
https://doi.org/10.7554/eLife.75526
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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

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Gökçe Senger

    Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
    Competing interests
    The authors declare that no competing interests exist.

  2. Stefano Santaguida

    Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1501-6190

  3. Martin H Schaefer

    Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
    For correspondence
    martin.schaefer@ieo.it
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7503-6364

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.

Reviewing Editor

  1. Elana J Fertig, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, United States

Version history

  1. Received: November 12, 2021
  2. Preprint posted: December 9, 2021 (view preprint)
  3. Accepted: May 13, 2022
  4. Accepted Manuscript published: May 16, 2022 (version 1)
  5. Version of Record published: May 26, 2022 (version 2)

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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  1. Gökçe Senger
  2. Stefano Santaguida
  3. Martin H Schaefer
(2022)
Regulation of protein complex partners as a compensatory mechanism in aneuploid tumors
eLife 11:e75526.
https://doi.org/10.7554/eLife.75526

Share this article

https://doi.org/10.7554/eLife.75526

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