Systemic Alterations of Cancer Cells and Their Boost by Polyploidization: Unicellular Attractor (UCA) Model

Area of Science:

• Evolutionary Biology
• Genetics
• Cancer Biology

Background:

• Existing theories on cancer development, including atavistic reversal, cancer attractors, somatic mutation, genome chaos, and tissue organization fields, offer fragmented insights.
• The 'atavistic reversal' theory serves as a foundational concept for understanding evolutionary shifts in cellular behavior.

Purpose of the Study:

• To introduce a unified unicellular attractor (UCA) model integrating key cancer development theories.
• To elucidate the evolutionary trajectory of the human interactome and its relation to cellular attractors.
• To explore the role of cellular stress and genetic alterations in activating the unicellular attractor.

Main Methods:

• Meta-analyses to integrate existing theories into the UCA model.
• Analysis of human interactome evolutionary growth from core to periphery.
• Modeling of random walks on protein interaction networks to simulate genetic and epigenetic changes.
• Functional enrichment analysis of cancer cell gene expression.

Main Results:

• The UCA model integrates diverse cancer theories, with 'atavistic reversal' as a keystone.
• The human interactome shows gradual core-to-periphery evolutionary growth, with higher protein interaction density in the UC center.
• Cellular stress and genetic/epigenetic alterations can gradually activate the UC center, particularly during proliferation.
• Cancer cells exhibit hyperactivated energetics and suppressed multicellular genes, promoting selfish behavior, further amplified by polyploidization.

Conclusions:

• The UCA model provides a cohesive framework for understanding oncogenesis.
• Activation of the UC center through evolutionary and stress-induced mechanisms drives cancer development.
• The UCA model may guide the development of novel therapeutic strategies targeting cancer's fundamental mechanisms.