PTEN expression can be used as a switch between senescence and apoptosis in breast cancer cells according to a logical model of the G2/M checkpoint

Author(s)

Marcello, Yolanda M. B. ; Silveira, Daner A. ; Gupta, Shantanu ; Mombach, Jose Carlos M.

• Document type: Journal article
• Source: BIOSYSTEMS; v. 235, p. 6-pg., 2023-12-07.

Abstract

Worldwide, the second-highest mortality rate is caused by breast cancer (BC). The most studied BC cell line is MCF-7 because it exhibits strong consistency with clinical cases and is a good system for analyzing tumors with functional estrogen receptors (ER-positive cancers). In this paper, we introduce the first theoretical method for describing PTEN-loss-induced cellular senescence (PICS), which is an increase in cellular senescence caused by PTEN knockout, utilizing a logical model of the G2/M checkpoint. We predict that PTEN expression acts as a switch between cell phenotypes associated with senescence and apoptosis. We show that PICS is induced by the activity of the positive feedback between AKT and mTORC2, and that overexpression of PTEN will disrupt the feedback, abrogating senescence and only leading to arrest or apoptosis. Furthermore, we demonstrate that miR-21 can be used as a target against proliferation control because its knockout is equivalent to PTEN overexpression. We think the findings can be used to motivate new strategies for MCF-7 strain proliferation control. (AU)

• FAPESP's process: 21/09070-8 - Modeling, analysis, and inference of biological networks
• Grantee: Shantanu Gupta
• Support Opportunities: Scholarships in Brazil - Post-Doctoral