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Live and let die: signaling AKTivation and UPRegulation dynamics in SARS-CoVs infection and cancer

Mariana Suaya1,2, Gonzalo Manuel Sánchez1,2, Antonella Vila1,2

  • 1Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales (FCEN), Universidad de Buenos Aires (UBA), Buenos Aires, Argentina.

Cell Death & Disease
|October 3, 2022
PubMed

Insights

The AKT and Unfolded Protein Response (UPR) pathways control cell survival and death, crucial in SARS-CoV-2 infection and cancer. Their crosstalk offers a unified target for new antiviral and anticancer therapies, potentially using drug repositioning.

Area of Science:

  • Molecular Biology
  • Virology
  • Oncology

Background:

  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, impacting cell survival and death.
  • The AKT and Unfolded Protein Response (UPR) pathways are vital for cell homeostasis and are implicated in viral infections and cancer.
  • Cancer is a major comorbidity of COVID-19, highlighting the need to understand shared molecular mechanisms.

Purpose of the Study:

  • To review the roles of AKT and UPR pathways in SARS-CoV-2 infection.
  • To examine the involvement of AKT and UPR pathways in cancer development and progression.
  • To explore the crosstalk between AKT and UPR pathways as a potential therapeutic target.

Main Methods:

  • Literature review of existing research on AKT and UPR pathways.
  • Analysis of molecular mechanisms linking these pathways to SARS-CoV-2 infection.
  • Investigation of the pathways' roles in tumorigenesis and progression.

Main Results:

  • The AKT and UPR pathways are deregulated during SARS-CoV-2 infection and in cancer.
  • Evidence suggests a unified homeostatic control system involving crosstalk between AKT and UPR.
  • Feedback regulation between these pathways is a master control of cell fate (survival/death).

Conclusions:

  • The interaction between AKT and UPR pathways is a critical regulator of cell survival and death.
  • This crosstalk represents a promising therapeutic target for both SARS-CoV-2 infection and cancer.
  • Drug repositioning offers a cost-effective strategy for developing treatments targeting these pathways.

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