Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 May 12;16(1):730.
doi: 10.1007/s12672-025-02512-4.

PTTG1 promotes M2 macrophage polarization via the cGMP-PKG signaling pathway and facilitates EMT progression in human epithelial ovarian cancer cells

Liang Tian  1   2 , Liyun Liu  3 , Chunlou Wang  2 , Yan Kong  4 , Zhigang Miao  2 , Qing Yao  2 , He Zhang  2 , Yuehong Li  5
Affiliations

PTTG1 promotes M2 macrophage polarization via the cGMP-PKG signaling pathway and facilitates EMT progression in human epithelial ovarian cancer cells

Liang Tian et al. Discov Oncol. .

Abstract

Epithelial Ovarian Cancer (EOC) is complex and heterogeneous, making accurate prognosis and treatment prediction difficult. New therapeutic targets and their mechanisms are urgently needed. This study explored the role of PTTG1 in ovarian cancer via the cGMP-PKG signaling pathway, focusing on its effects on M2 macrophage polarization and EMT progression in EOC cells. Using the GSE135886 database, we performed differential gene expression, pathway enrichment, and immune infiltration analyses to identify key targets influencing EMT and macrophage polarization. We then constructed PTTG1 knockdown and overexpression cell lines to assess the impact of PTTG1 on cell proliferation, migration, invasion, EMT, and macrophage polarization in vitro. Analysis revealed that differentially expressed genes were enriched in the cGMP-PKG pathway and correlated with M2 macrophages. PTTG1 overexpression in A2780 and SK-OV-3 ovarian cancer cells promoted proliferation, invasion, and migration, while enhancing sGC, PKG1, and PKG2 expression to activate the cGMP-PKG pathway and induce M2 macrophage polarization. PTTG1 knockdown produced opposite results, reinforcing our conclusions. This study uncovers a novel mechanism of PTTG1 in ovarian cancer development and suggests it as a potential therapeutic target.

Keywords: CGMP-PKG signaling pathway; Epithelial-mesenchymal transition; Macrophage polarization; Ovarian cancer; PTTG1.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethics approval and consent to participate: Does not apply. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Screening of differentially expressed genes in different grades of ovarian cancer in the GSE135886 database through the online database. A Principal component analysis (PCA) of dataset. B Heat map of the top differentially expressed genes. C Volcano plots of differentially expressed genes in different grades of ovarian cancer compared using pairwise comparisons. D Venn diagram of intersecting genes. E GO functional enrichment analysis of intersecting genes. F KEGG functional enrichment analysis of intersecting genes. G Analysis of differentially expressed genes in immune cells. H PPI analysis of differentially expressed genes related to macrophages
Fig. 2
Fig. 2
Construction of PTTG1 overexpression and knockdown cell lines. Transfection with overexpression vectors and siRNA sequences in SK-OV-3 and A2780 cells and incubation for 48 h. A Relative expression of PTTG1 protein was detected by western blotting. B Detection of relative expression levels of PTTG1 mRNA by RT-qPCR. (Compared between the two groups, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001)
Fig. 3
Fig. 3
PTTG1 can induce proliferation, invasion and migration of ovarian cancer cells. A Transfection of overexpression vectors and siRNA sequences in SK-OV-3 and A2780 cells, incubation for 0, 24, 48, and 72 h, and detection of changes in cell viability the CCK8 experiment. B Detection of changes in the proliferative ability of SK-OV-3 and A2780 cells using a plate clone formation experiment. C Changes in the migration abilities of SK-OV-3 and A2780 cells were detected using a cell scratch experiment. D Detection of changes in the invasion ability of SK-OV-3 and A2780 cells by transwell assay
Fig. 4
Fig. 4
PTTG1 can activate the cGMP-PKG signaling pathway. Transfection with overexpression vectors and siRNA sequences in SK-OV-3 and A2780 cells and incubation for 48 h. Relative expression levels of PTTG1, sGC, PKG2, and PKG1 proteins were detected by western blotting. (Compared between the two groups, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001)
Fig. 5
Fig. 5
PTTG1 can induce the positive proportion of CD206 and CD163 in THP-1 cells. Transfection with overexpression vectors and siRNA sequences in SK-OV-3 and A2780 cells and incubation for 48 h. Changes in the proportion of positive cells of CD206 and CD163 by flow cytometry. (Compared between the two groups, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001)
Fig. 6
Fig. 6
PTTG1 can enhance the protein and mRNA expression levels of CD206 and CD163 in THP-1 cells. Transfection with overexpression vectors and siRNA sequences in SK-OV-3 and A2780 cells and incubation for 48 h. The relative expression levels of proteins and mRNA of CD206 and CD163 by Western blotting and RT-qPCR. (Compared between the two groups, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001)
See this image and copyright information in PMC

References

    1. Feng X, Zahed H, Onwuka J, Callister MEJ, Johansson M, Etzioni R, et al. Cancer stage compared with mortality as end points in randomized clinical trials of cancer screening: a systematic review and meta-analysis. JAMA. 2024;331(22):1910–7. 10.1001/jama.2024.5814. - PMC - PubMed
    1. Dalmartello M, La Vecchia C, Bertuccio P, Boffetta P, Levi F, Negri E, et al. European cancer mortality predictions for the year 2022 with focus on ovarian cancer. Ann Oncol Off J Eur Soc Med Oncol. 2022;33(3):330–9. 10.1016/j.annonc.2021.12.007. - PubMed
    1. Webb PM, Jordan SJ. Global epidemiology of epithelial ovarian cancer. Nat Rev Clin Oncol. 2024;21(5):389–400. 10.1038/s41571-024-00881-3. - PubMed
    1. Kuroki L, Guntupalli SR. Treatment of epithelial ovarian cancer. BMJ. 2020;371:m3773. 10.1136/bmj.m3773. - PubMed
    1. Erin N, Grahovac J, Brozovic A, Efferth T. Tumor microenvironment and epithelial mesenchymal transition as targets to overcome tumor multidrug resistance. Drug Resistance Updates Rev Comment Antimicrob Anticancer Chemother. 2020;53:100715. 10.1016/j.drup.2020.100715. - PubMed

LinkOut - more resources