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Article

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

by
Kholoud Alwosaibai
1,2,3,*,
Barbara C. Vanderhyden
2,3,4,
Fatimah A. Alsaffar
5,
Salma Alamri
1 and
Abdulaziz A. Almotlak
6
1
Biomedical Research Department, Research Center, King Fahad Specialist Hospital-Dammam, Eastern Health Cluster, Dammam 32253, Saudi Arabia
2
Departments of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
3
Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada
4
Department of Obstetrics and Gynecology, University of Ottawa, Ottawa, ON K1H 8L6, Canada
5
Medical Laboratory Science Department, AlGhad College for Applied Medical Sciences, Dammam 32423, Saudi Arabia
6
Department of Pharmacology, Imam Abdulrahman bin Faisal University, Dammam 31441, Saudi Arabia
*
Author to whom correspondence should be addressed.
Cancers 2025, 17(20), 3317; https://doi.org/10.3390/cancers17203317 (registering DOI)
Submission received: 3 September 2025 / Revised: 2 October 2025 / Accepted: 6 October 2025 / Published: 14 October 2025
(This article belongs to the Special Issue Tumor Microenvironment of Gynecological Tumors)

Simple Summary

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.

Abstract

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.
Keywords: fallopian tube; oviduct; ovarian cancer; epithelial cells; stem cells; epithelial–mesenchymal transition; EMT; P53; BRCA1; CD44 fallopian tube; oviduct; ovarian cancer; epithelial cells; stem cells; epithelial–mesenchymal transition; EMT; P53; BRCA1; CD44

Share and Cite

MDPI and ACS Style

Alwosaibai, K.; Vanderhyden, B.C.; Alsaffar, F.A.; Alamri, S.; Almotlak, A.A. P53 Mutation Induces Epithelial-to-Mesenchymal Transition (EMT) Associated with Stem Cell Properties and Tumorigenesis in Fallopian Tube Cells. Cancers 2025, 17, 3317. https://doi.org/10.3390/cancers17203317

AMA Style

Alwosaibai K, Vanderhyden BC, Alsaffar FA, Alamri S, Almotlak AA. P53 Mutation Induces Epithelial-to-Mesenchymal Transition (EMT) Associated with Stem Cell Properties and Tumorigenesis in Fallopian Tube Cells. Cancers. 2025; 17(20):3317. https://doi.org/10.3390/cancers17203317

Chicago/Turabian Style

Alwosaibai, Kholoud, Barbara C. Vanderhyden, Fatimah A. Alsaffar, Salma Alamri, and Abdulaziz A. Almotlak. 2025. "P53 Mutation Induces Epithelial-to-Mesenchymal Transition (EMT) Associated with Stem Cell Properties and Tumorigenesis in Fallopian Tube Cells" Cancers 17, no. 20: 3317. https://doi.org/10.3390/cancers17203317

APA Style

Alwosaibai, K., Vanderhyden, B. C., Alsaffar, F. A., Alamri, S., & Almotlak, A. A. (2025). P53 Mutation Induces Epithelial-to-Mesenchymal Transition (EMT) Associated with Stem Cell Properties and Tumorigenesis in Fallopian Tube Cells. Cancers, 17(20), 3317. https://doi.org/10.3390/cancers17203317

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