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Ecological network analysis reveals cancer-dependent chaperone-client interaction structure and robustness

Author

Listed:
  • Geut Galai

    (Ben-Gurion University of the Negev)

  • Xie He

    (Dartmouth College)

  • Barak Rotblat

    (Ben-Gurion University of the Negev
    The National Institute for Biotechnology in the Negev)

  • Shai Pilosof

    (Ben-Gurion University of the Negev)

Abstract

Cancer cells alter the expression levels of metabolic enzymes to fuel proliferation. The mitochondrion is a central hub of metabolic reprogramming, where chaperones service hundreds of clients, forming chaperone-client interaction networks. How network structure affects its robustness to chaperone targeting is key to developing cancer-specific drug therapy. However, few studies have assessed how structure and robustness vary across different cancer tissues. Here, using ecological network analysis, we reveal a non-random, hierarchical pattern whereby the cancer type modulates the chaperones’ ability to realize their potential client interactions. Despite the low similarity between the chaperone-client interaction networks, we highly accurately predict links in one cancer type based on another. Moreover, we identify groups of chaperones that interact with similar clients. Simulations of network robustness show that this group structure affects cancer-specific response to chaperone removal. Our results open the door for new hypotheses regarding the ecology and evolution of chaperone-client interaction networks and can inform cancer-specific drug development strategies.

Suggested Citation

  • Geut Galai & Xie He & Barak Rotblat & Shai Pilosof, 2023. "Ecological network analysis reveals cancer-dependent chaperone-client interaction structure and robustness," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41906-2
    DOI: 10.1038/s41467-023-41906-2
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