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

Abstrakt

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 feedback typically
lasting a few hours as a feature of the genome regulation by self-organising criticality.
It involves the rapid splitting of the pericentromeric heterochromatin clusters, the 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 the breast cancer cell line resistant to doxorubicin. The adaptability of
aggressive cancer to treatments can be explained by emergent stress response evolutionarily
protecting reproduction.