Suppressing Expression of SERPINE1/PAI1 Through Activation of GPER1 Reduces Progression of Vulvar Carcinoma - Abstract

Sep 21, 2026

Upload by Skyler

Study investigates how SERPINE1/PAI1 influences vulvar cancer cell proliferation, migration, and invasion, and whether PAI1 acts as oncogene or tumor suppressor. VC cells were treated with GPER1 agonist G1 or antagonist G36 to modulate SERPINE1 expression, combined with forward transfection knockdown. Proliferation was assessed by resazurin assay; migration by gap closure; clonogenicity by colony and tumor sphere formation; protein levels by western blots. In A431 cells, PAI1 reduction decreased migration, proliferation, and colony growth, while G36 increased PAI1 and malignant phenotypes in CAL39. Results suggest suppressing PAI1 can reduce VC progression and tumorigenic potential, positioning GPER1 as a target.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages14

Reading Time35 min

AccessFree to download

Abstract

Background/Aim

Materials and Methods

Results

Conclusion

CANCER GENOMICS & PROTEOMICS 21: 566-579 (2024) doi:10.21873/cgp.20473 Suppressing Expression of SERPINE1/PAI1 Through Activation of GPER1 Reduces Progression of Vulvar Carcinoma TAMMY DOELKER, JULIA GALLWAS and CARSTEN GRÜNDKER University Medical Center Göttingen, Department of Gynecology and Obstetrics, Göttingen, Germany Abstract. Background/Aim: The serine proteinase inhibitor 1 (SERPINE1) gene codes for the plasminogen activator inhibitor 1 (PAI1) protein and is thought to play a tumor supportive role in various cancers. In this work we aimed to uncover the role PAI1 plays in the proliferation, migration, and invasion of vulvar cancer (VC), and define the protein’s function as an oncogene or tumor suppressor. Materials and Methods: Through treatment with an agonist (G1) and antagonist (G36) of G-coupled estrogen receptor 1 (GPER1), an upstream regulator of SERPINE1 expression, and a forward transfection knockdown protocol, the expression of SERPINE1/PAI1 in VC cells was altered. The effects these altered SERPINE1/PAI1 levels had on tumor cell functions were then examined. Proliferation was analyzed using the resazurin assay, while migration was studied via the gap closure assay. Through colony-and tumor sphere-formation assays clonogenicity was tested, and western blots showed protein expression. Results: In A431 VC cells, when the levels of PAI1 were reduced via knockdown or treatment with G1, migration, proliferation, and colony growth was reduced. Treatment with G36 increased expression of PAI1 and increased migration and colony size in CAL39 cells. Conclusion: Based on the findings in this study, suppressing PAI1 expression in VC cells appears to reduce their progression and tumorigenic potential. Therefore, PAI1 could possibly function as an oncogene in VC. GPER1 appears to bea suitable target for suppressing PAI1 in VC. Correspondence to: Carsten Gründker, Department of Gynecology and Obstetrics, Robert-Koch-Str. 40, 37075 Göttingen, Germany. Tel: +49 (0)5513969810, e-mail: [grundker@med.uni-goettingen.de](grundker@med.uni-goettingen.de) [Key Words:](Key Words: Serpin family E member 1)[ Serpin family E member 1](Key Words: Serpin family E member 1) , SERPINE1, plasminogen activator inhibitor 1, PAI1, G-coupled estrogen receptor 1, GPER1, vulvar carcinoma, oncogene. ©2024 The Author(s) . Published by the International Institute of Anticancer Research. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license ([https://creativecommons.org/licenses/by-nc-nd/4.0](https://creativecommons.org/licenses/by-nc-nd/4.0)). Vulva cancer (VC) is an uncommon yet relevant gynecological cancer, diagnosed in roughly 45,000 new patients worldwide and resulting in 17,000 deaths every year (1) . Most VC are squamous cell carcinomas (SCC) in older women, unassociated with human papillomavirus (HPV) infection. In younger women diagnosed with SCC, the tumors are more frequently related to a high-risk type of HPV (2, 3) . Other, rarer forms of VCs include adenocarcinoma, melanoma, and sarcoma although they account for a far less significant number of cancers (2, 3) . The established vulvar SCC (VSCC) cell lines A431 and CAL39 are both HPV negative and as the most common form of VC, were selected as the focus of this study. Surgical excision is currently the treatment standard for VC. Adjuvant radiochemotherapy or chemoradiotherapy is indicated in cases where clear margins cannot be achieved with surgery alone, or in tumors that have metastasized to regional or distant lymph nodes (4) . With an increasing number of diagnoses in younger women, an aging population contributing to a rise in incidence, and VC patients experiencing the longest delay in diagnosis of all gynecological malignancies, now more than ever, an essential point of research is understanding the pathways involved in the aggressive features of VC at all stage

FAQs

What role does SERPINE1/PAI1 play in vulvar cancer according to this study?

The study aims to determine whether PAI1 supports tumor progression. Findings indicate that suppressing PAI1 reduces migration, proliferation, and colony growth in vulvar carcinoma cells, consistent with an oncogenic role.

How did the researchers modulate SERPINE1/PAI1 expression?

GPER1 was targeted using the agonist G1 and antagonist G36, which act as upstream regulators of SERPINE1 expression. A forward transfection knockdown protocol further reduced SERPINE1/PAI1 levels in VC cells.

What were the main experimental readouts for tumor cell behavior?

Cell proliferation was measured with the resazurin assay, migration with the gap closure assay, and clonogenicity with colony and tumor sphere formation assays. Western blots were used to assess protein expression.

Sep 21, 2026

Upload by Skyler