On p21 tracking property in cancer cell unravelled bio-digitally in silico. Are apoptosis principles universal?

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Strategies for Tracking Anastasis, A Cell Survival Phenomenon that Reverses Apoptosis

Published on: February 16, 2015

R M Ardito Marretta1, G Barbaraci

  • 1Department of Structural, Aerospace Engineering and Geotechnics, University of Palermo, Viale delle Scienze, Block 8, 90128, Palermo, Italy. romario@unipa.it

Molecular & Cellular Biomechanics : MCB
|December 15, 2010
PubMed

Insights

p21 protein normally halts cell division and triggers apoptosis. In cancer, its irregular mRNA dynamics disrupt this, aiding proliferation, but new mechanisms can restore apoptosis.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Signaling

Background:

  • Severe DNA damage activates p21, inhibiting cell cycle (G2/M transition) and promoting apoptosis via retinoblastoma protein, E2F1, and APAF1.
  • Mechanisms underlying apoptosis failure in proliferating cancer cells remain unclear.
  • The p21/p53/Mdm2 network typically exhibits a digital response in cancer cells.

Purpose of the Study:

  • To investigate the role of p21 mRNA dynamics in apoptosis failure during cancer cell proliferation.
  • To elucidate the mechanisms by which cancer cells evade apoptosis.
  • To identify strategies for re-establishing a stable apoptotic phase in cancer cells.

Main Methods:

  • Development of an original cell signaling-protein simulator.
  • In silico simulation of protein interactions and signaling pathways.
  • Analysis of p21 mRNA dynamics and its correlation with apoptosis.

Main Results:

  • Apoptosis phase instability in cancer cells is directly linked to irregular p21 mRNA dynamics, operating under a 'tracking memory' principle.
  • p21 mRNA paradoxically decouples from its target genes, facilitating cancer cell proliferation.
  • Mechanisms enabling cancer cells to re-enter a stable apoptosis phase were identified.

Conclusions:

  • Aberrant p21 mRNA dynamics are a key factor in cancer cell apoptosis evasion and proliferation.
  • The 'tracking memory' principle in p21 mRNA regulation contributes to cancer progression.
  • Targeting these identified mechanisms offers potential therapeutic strategies to restore apoptosis in cancer.

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