Related Experiment Video
Updated: Jun 25, 2025
Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer
Published on: August 2, 2024
Immunoreactive Microenvironment Modulator GBP5 Suppresses Ovarian Cancer Progression by Inducing Canonical Pyroptosis
Chang Zou1, Jiacheng Shen1, Fangfang Xu1
1Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 200092, China.
Abstract:
Ovarian cancer has the highest mortality among gynecological malignancies, and exploring effective strategies to reverse the immunosuppressive tumor microenvironment in patients remains a pressing scientific challenge. In this study, we identified a pyroptosis-related protective factor, GBP5, which significantly inhibits the growth of ovarian cancer cells and patient-derived ovarian cancer organoids, impeding the invasion and migration of ovarian cancer cells. Results of immunohistochemistry and external single-cell data verification were consistent. Further research confirmed that GBP5 in ovarian cancer cell can induce canonical pyroptosis through JAK2/STAT1 pathway, thereby restraining the progression of ovarian cancer. Interestingly, in this study, we also discovered that ovarian cancer cells with high GBP5 expression exhibit increased expressions of CXCL9/10/11 in a co-culture assay. Subsequent immune cell infiltration analyses revealed the remodeling of immunosuppressive microenvironment in ovarian cancer patients, characterized by increased infiltration and polarization of M1 macrophages. External immunotherapy database analysis showed profound potential for the application of GBP5 in immunotherapy strategies for ovarian cancer. Overall, our study demonstrates that the protective factor GBP5 significantly inhibits ovarian cancer progression, triggering canonical pyroptosis through the JAK2-STAT1 pathway. Driven by its pro-inflammatory nature, it can also enhance M1 macrophages polarization and reverse immunosuppressive microenvironment, thus providing new insights for ovarian cancer treatment.
Insights
Guanylate-binding protein 5 (GBP5) inhibits ovarian cancer growth and metastasis by inducing pyroptosis via the JAK2/STAT1 pathway. GBP5 also enhances M1 macrophage polarization, reversing the immunosuppressive tumor microenvironment for potential ovarian cancer immunotherapy.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Ovarian cancer presents a high mortality rate among gynecological malignancies.
- Reversing the immunosuppressive tumor microenvironment is crucial for effective ovarian cancer treatment.
Purpose of the Study:
- To investigate the role of Guanylate-binding protein 5 (GBP5) in ovarian cancer.
- To elucidate the mechanisms by which GBP5 affects ovarian cancer progression and the tumor microenvironment.
Main Methods:
- Immunohistochemistry and single-cell data analysis were used to verify GBP5 expression.
- JAK2/STAT1 pathway activation was studied in relation to GBP5-induced pyroptosis.
- Co-culture assays and immune cell infiltration analyses were performed to assess microenvironmental changes.
- External immunotherapy databases were analyzed for potential therapeutic applications.
Main Results:
- GBP5 significantly inhibits ovarian cancer cell growth, invasion, and migration.
- GBP5 induces canonical pyroptosis through the JAK2/STAT1 pathway, restraining cancer progression.
- High GBP5 expression correlates with increased CXCL9/10/11 expression and M1 macrophage polarization.
- GBP5 was found to remodel the immunosuppressive tumor microenvironment.
Conclusions:
- GBP5 acts as a protective factor against ovarian cancer progression.
- GBP5-mediated pyroptosis and immune microenvironment remodeling offer novel therapeutic strategies for ovarian cancer.
- GBP5 holds significant potential for application in ovarian cancer immunotherapy.
More Related Videos
09:08Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
Published on: January 12, 2020
06:12Author Spotlight: THP-1 Macrophage Response to LPS/ATP — Unveiling the Pyroptosis, Apoptosis, and Necroptosis Spectrum
Published on: May 3, 2024
Related Concept Videos
01:31The Intrinsic Apoptotic Pathway
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
02:23Abnormal Proliferation
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...