Self-organisation of early stress response in the biology of cancer


  • Jekaterina Erenpreisa Latvian Biomedical Research and Study Centre
  • Kristine Salmina Latvian Biomedical Research and Study Centre
  • Ninel M Vainshelbaum Latvian Biomedical Research and Study Centre
  • Inna Inashkina Latvian Biomedical Research and Study Centre
  • Talivaldis Freivalds Institute of Cardiology and Regenerative Medicine, University of Latvia



The early stress response by AP-1 (FOS/JUN), supported by upregulation of c-Myc and involved in cell-fate changes and adaptation to hostile environments, is increased in cancer. The review shows the biphasic character of this response with negative feed-back typically lasting a few hours as a feature of the genome regulation by self-organising criticality. It involves  rapid splitting of the pericentromeric heterochromatin clusters, opening of the active chromatin, and a massive transcription acceleration wave. Phylostratigraphic analysis revealed that AP-1 genes evolved in the Cambrian explosion ~500 Mya integrating the protein interaction networks of reproduction including proto-placenta intertwined with cytokine and immunity pathways, sex determination, oocyte maturation, and embryonal stemness. The peak  of this response as part of accelerated cell senescence led by AP-1 and IL-1β was found in breast cancer cell-line resistant to doxorubicin. Adaptability of aggressive cancer to treatments can be explained by emergent stress response evolutionarily protecting reproduction


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