# TAp73 modulates proliferation and ferroptosis in mammary epithelial cells

## TL;DR

TAp73, a protein linked to p73, controls cell growth and a type of cell death called ferroptosis in mammary cells, offering new insights into epithelial cell regulation.

## Contribution

TAp73 is shown to regulate both proliferation and ferroptosis in epithelial cells, revealing a novel dual function.

## Key findings

- TAp73 overexpression inhibits cell proliferation by increasing p21 levels.
- TAp73 enhances ferroptosis by upregulating PTGS2 and TFRC genes.
- TAp73 knockdown reduces ferroptosis and oxidative stress in epithelial cells.

## Abstract

TAp73, a transcriptionally active isoform of the p73 gene, is essential for epithelial tissue development. Ferroptosis, a regulated form of cell death characterized by lipid peroxidation and reactive oxygen species (ROS) accumulation, has been increasingly studied in recent years. However, its role in epithelial cells and the regulatory function of TAp73 in this context remain poorly understood.

We investigated the role of TAp73 in epithelial cell proliferation and ferroptosis using ectopic overexpression and RNA interference approaches. Cell proliferation was assessed through colony formation and DNA synthesis assays. Ferroptosis was induced using RSL3, and the effects were evaluated by measuring cell viability, ROS levels, and the expression of ferroptosis-associated genes PTGS2 and TFRC.

TAp73 overexpression significantly increased p21 expression, suppressed colony formation and DNA synthesis, thereby inhibiting cell proliferation. In contrast, TAp73 knockdown reduced p21 levels and enhanced cell proliferation. RSL3 treatment induced a dose-dependent increase in cell death and ROS accumulation, confirming the susceptibility of epithelial cells to ferroptosis. Furthermore, TAp73 overexpression enhanced RSL3-induced ferroptosis by upregulating PTGS2 and TFRC, while TAp73 knockdown diminished their expression, reducing oxidative stress and lipid peroxidation.

TAp73 acts as a dual regulator of epithelial cell fate by inhibiting proliferation and promoting ferroptosis. These findings reveal a novel role for TAp73 in epithelial cell biology and suggest potential therapeutic targets for diseases involving epithelial cell death.