# P53 Mutation Induces Epithelial-to-Mesenchymal Transition (EMT) Associated with Stem Cell Properties and Tumorigenesis in Fallopian Tube Cells

## TL;DR

This study shows that P53 mutations in fallopian tube cells lead to cancer-like changes, suggesting a role in early ovarian cancer development.

## Contribution

The study reveals that Trp53 loss induces EMT and stem cell traits in fallopian tube cells, potentially initiating ovarian cancer.

## Key findings

- Loss of Trp53 in fallopian tube cells leads to increased growth, migration, and epithelial-to-mesenchymal transition.
- Combining Trp53 and Brca1 mutations enhances cell growth and migration, suggesting a role in cancer progression.
- Trp53 mutations may drive the formation of precursor lesions in the fallopian tube, linked to ovarian cancer initiation.

## Abstract

Ovarian cancer, particularly high-grade serous carcinoma, is one of the most aggressive and lethal gynecological cancers. Increasing evidence suggests that many of these tumors may begin in the fallopian tube, but the exact role of genetic mutations in this process is not fully understood. In this study, we explored how the loss of two well-known tumor suppressor genes, Trp53 and Brca1, affect normal fallopian tube cells. We found that loss of Trp53 caused these cells to grow faster, migrate more, and develop features of stem cells and epithelial-to-mesenchymal transition, changes that may allow them to act as early cancer-initiating cells. While BRCA1 loss alone did not strongly alter cell behavior, its combination with P53 loss further promoted cell growth and migration. These findings highlight the critical role of P53 in early ovarian cancer initiation and suggest that Brca1 mutations may accelerate disease progression rather than initiate it.

Background/Objectives: Type II ovarian cancer, including high-grade serous carcinoma (HGSC), is genetically unstable and exhibits frequent mutations in the tumor suppressor genes. Mutations of TP53 and BRCA1 genes have been associated with HGSC, which has been suggested as a subtype that arises from the fallopian tube lesion called serous tubal intraepithelial carcinoma (STIC). Although TP53 and BRCA1 genes are well-known tumor suppressor genes, the actual effects of TP53 and BRCA1 mutations in enhancing the development of ovarian cancer initiated from STIC are poorly understood. Methods: In this study, we knocked out Trp53 and Brca-1 in epithelial cell clones derived from mice fallopian tube tissues (known as oviducts) and investigated the potential involvement of these two mutations in inducing cancer stem-like cells as cancer-initiating cells. Results: We have shown that the knockout of Trp53 induced oviduct cells to undergo EMT and acquire stem cell characteristics. Conclusions: Trp53 mutation may induce the early stage of precursor lesions formation at the distal end of the oviducts.