Network of migrating cells in the uterus, interconnected by TGF-β1 signaling pathways.

Endometriosis Breakthrough: How TGF-β1 and OCT4 Fuel Cell Migration

Jordan Keane in Health & Wellness August 2025 • 5 min read.

"Unlocking the Secrets of Endometriosis: New Research Reveals Key Molecular Players in Cell Migration"

Endometriosis, a chronic condition affecting millions of women worldwide, is characterized by the growth of endometrial-like tissue outside the uterus. This misplaced tissue can lead to a host of painful and disruptive symptoms, including pelvic pain, heavy bleeding, and infertility. While the exact causes of endometriosis remain elusive, recent research is shedding light on the complex molecular mechanisms that drive its progression.

One area of intense investigation is the role of transforming growth factor-beta (TGF-β), a signaling protein known to influence cell growth, differentiation, and migration. Elevated levels of TGF-β have been found in the peritoneal fluid and endometriotic tissues of women with endometriosis, suggesting its involvement in the disease process. Adding another layer of complexity, the pluripotent transcription factor OCT4, typically associated with stem cells and early development, is also found at higher levels in endometriotic tissues.

A new study published in PLOS ONE delves deeper into the interplay between TGF-β1, a specific form of TGF-β, and OCT4 in the context of endometriosis. By examining tissue samples and conducting in vitro experiments, the researchers uncovered a compelling link between these two factors and the enhanced cell migration observed in endometriosis. This discovery offers potential new targets for therapeutic intervention.

TGF-β1 and OCT4: The Dynamic Duo Driving Endometriosis Cell Migration

Network of migrating cells in the uterus, interconnected by TGF-β1 signaling pathways.

The research team began by analyzing endometrial tissue samples from women with and without endometriosis. They categorized tissues based on their migratory capacity: high-migratory samples from women with adenomyotic myometrium (a condition where endometrial tissue grows into the uterine muscle) and chocolate cysts (ovarian cysts filled with old blood), and low-migratory samples from healthy or hyperplastic endometrium. The results revealed a significant difference: the high-migratory ectopic endometriotic tissues exhibited markedly higher mRNA levels of both TGF-β receptor I (TGF-β RI) and OCT4 compared to the low-migratory tissues.

This initial finding suggested a connection, which the researchers further explored by analyzing the correlation between TGF-β RI, OCT4, and several migration-related genes – SNAIL, SLUG, and TWIST. These genes are known to play a role in epithelial-mesenchymal transition (EMT), a process where cells lose their cell-to-cell adhesion and gain migratory properties, frequently observed in cancer and implicated in endometriosis. The analysis revealed positive correlations between TGF-β RI and OCT4, as well as between either TGF-β RI or OCT4 and the migration-related genes. This supported the hypothesis that TGF-β and OCT4 are working together to promote cell migration through pathways involving SNAIL, SLUG, and TWIST.

TGF-β1 Boosts OCT4: In vitro experiments showed that TGF-β1 dose-dependently increased the levels of OCT4 mRNA and protein.
SNAIL and N-CAD Join the Party: TGF-β1 also upregulated SNAIL and N-Cadherin (N-CAD), proteins associated with EMT and cell migration.
OCT4 is Key: Silencing OCT4 significantly reduced the TGF-β1-induced expression of N-CAD and SNAIL, suggesting that OCT4 is a crucial mediator of TGF-β1's effects.

To directly assess the impact of OCT4 on cell migration, the researchers conducted wound-closure and transwell migration assays. In the wound-closure assay, a scratch was made in a layer of endometriotic cells, and the rate at which the cells migrated to close the gap was measured. In the transwell assay, cells were placed in an upper chamber separated from a lower chamber by a membrane with small pores, allowing migratory cells to pass through. The results were clear: TGF-β1 significantly increased the migration ability of endometriotic cells, and silencing OCT4 dramatically suppressed this TGF-β1-induced cell migration. Confocal microscopy further revealed that OCT4 knockdown inhibited the formation of actin stress fibers, which are essential for cell movement.

Targeting the Niche: A New Hope for Endometriosis Treatment

This study provides compelling evidence that TGF-β1 plays a critical role in initiating the expression of the pluripotent transcription factor OCT4, which in turn promotes cell migration in endometriosis. By identifying this key signaling pathway, the researchers have opened new avenues for developing targeted therapies that could disrupt the TGF-β1/OCT4 axis and reduce the migration and growth of endometriotic lesions. While further research is needed to translate these findings into clinical applications, this study represents a significant step forward in our understanding of endometriosis and offers hope for more effective treatments in the future.

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This article is based on research published under:

DOI-LINK: 10.1371/journal.pone.0145256, Alternate LINK

Title: Tgf-Βi Regulates Cell Migration Through Pluripotent Transcription Factor Oct4 In Endometriosis

Subject: Multidisciplinary

Journal: PLOS ONE

Publisher: Public Library of Science (PLoS)

Authors: Heng-Kien Au, Jui-Hung Chang, Yu-Chih Wu, Yung-Che Kuo, Yu-Hsi Chen, Wei-Chin Lee, Te-Sheng Chang, Pei-Chi Lan, Hung-Chih Kuo, Kha-Liang Lee, Mei-Tsu Lee, Chii-Ruey Tzeng, Yen-Hua Huang

Published: 2015-12-16

Everything You Need To Know

What is the primary role of TGF-β1 in the context of endometriosis, and how does it contribute to the disease's progression?

TGF-β1, a specific form of transforming growth factor-beta, is a signaling protein found at elevated levels in the peritoneal fluid and endometriotic tissues of women with endometriosis. Research indicates that TGF-β1 plays a critical role in initiating the expression of OCT4, a pluripotent transcription factor. This action contributes to the enhanced cell migration observed in endometriosis. The study highlights TGF-β1's role in upregulating SNAIL and N-Cadherin, proteins associated with epithelial-mesenchymal transition (EMT) and cell migration, thereby promoting the growth and spread of endometrial-like tissue outside the uterus.

How does OCT4 influence the development of endometriosis, and what is its relationship with TGF-β1 in promoting cell migration?

OCT4, a pluripotent transcription factor typically associated with stem cells, is found at higher levels in endometriotic tissues. This study reveals that OCT4 is a crucial mediator of TGF-β1's effects. Specifically, TGF-β1 boosts OCT4 levels. When OCT4 is silenced, the TGF-β1-induced expression of N-Cadherin and SNAIL is significantly reduced, indicating that OCT4 is key in the signaling pathway. Furthermore, silencing OCT4 dramatically suppressed TGF-β1-induced cell migration, as demonstrated through wound-closure and transwell migration assays. This suggests that OCT4, activated by TGF-β1, directly contributes to the increased migration ability of endometriotic cells, which is a hallmark of endometriosis progression.

Can you explain the concept of epithelial-mesenchymal transition (EMT) and its connection to TGF-β1 and OCT4 in the context of endometriosis?

Epithelial-mesenchymal transition (EMT) is a cellular process where cells lose their cell-to-cell adhesion and gain migratory properties. In endometriosis, EMT is implicated in the spread of endometrial-like tissue outside the uterus. TGF-β1, through its influence on OCT4, upregulates proteins associated with EMT, such as SNAIL and N-Cadherin. The SNAIL, SLUG and TWIST genes are known to play a role in EMT, contributing to the enhanced cell migration. The positive correlations between TGF-β RI and OCT4, as well as between either TGF-β RI or OCT4 and the migration-related genes, support that TGF-β and OCT4 are working together to promote cell migration through pathways involving EMT.

What experimental methods were used to investigate the roles of TGF-β1 and OCT4 in endometriosis, and what were the key findings?

The researchers employed several methods. First, they analyzed endometrial tissue samples from women with and without endometriosis, categorizing them based on migratory capacity. High-migratory samples (from women with adenomyotic myometrium and chocolate cysts) showed higher mRNA levels of both TGF-β receptor I (TGF-β RI) and OCT4 compared to low-migratory samples. In vitro experiments demonstrated that TGF-β1 increased OCT4 mRNA and protein levels and upregulated SNAIL and N-Cadherin. Wound-closure and transwell migration assays confirmed that TGF-β1 increased the migration ability of endometriotic cells, and silencing OCT4 suppressed this. Confocal microscopy showed that OCT4 knockdown inhibited the formation of actin stress fibers, essential for cell movement. The key findings revealed a compelling link between TGF-β1, OCT4, and enhanced cell migration, highlighting a potential therapeutic target.

How could the findings related to TGF-β1 and OCT4 lead to new treatment strategies for endometriosis, and what are the implications for future research?

The study identifies the TGF-β1/OCT4 axis as a key signaling pathway in endometriosis. By disrupting this axis, researchers hope to develop targeted therapies that reduce the migration and growth of endometriotic lesions. Potential therapeutic strategies could involve inhibiting TGF-β1 or interfering with OCT4's function. This is a significant step forward in understanding the disease. Further research is needed to translate these findings into clinical applications. This could involve developing drugs that specifically target TGF-β1 or OCT4, or exploring other components of the signaling pathway. Future research will focus on validating these targets and determining the most effective methods for therapeutic intervention, offering hope for more effective treatments for endometriosis in the future.