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Published on: November 28, 2019
Migrasome regulator TSPAN4 shapes the suppressive tumor immune microenvironment in pan-cancer
Lin-Jian Wang1,2,3, Ruiyan Xu3, Yangyang Wu1
1Trauma Research Center, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
Background:
Migrasomes are newly identified organelles on the retracting fibers of migrating cells, involved in releasing signaling molecules, expelling damaged mitochondria, and facilitating intercellular communication through phagocytosis. TSPAN4, a key regulator of migrasome formation, is a valuable marker for visualizing these organelles. However, its role in cancer remains unclear.
Methods:
We analyzed TSPAN4 expression and its prognostic significance across multiple cancers using TCGA Pan-Cancer (PANCAN), and TCGA TARGET GTEx datasets. The relationship between TSPAN4 and tumor heterogeneity, stemness, and the immunosuppressive tumor microenvironment was explored through RNA-seq and scRNA-seq data. In addition, we examined TSPAN4's role in glioma, focusing on migrasome formation, cell proliferation, and macrophage polarization.
Results:
Our analysis reveals that TSPAN4 is aberrantly expressed in various tumors, likely linked to its methylation status. It correlates with tumor heterogeneity, stemness, and a suppressive immune microenvironment. In glioma, TSPAN4 enhances cell proliferation and promotes macrophage polarization toward the immunosuppressive M2 phenotype.
Conclusions:
TSPAN4, as a migrasome regulator, plays a crucial role in shaping the immunosuppressive tumor microenvironment in pan-cancer.
Insights
TSPAN4 regulates migrasomes and influences cancer. This protein impacts tumor heterogeneity, stemness, and the immune microenvironment, promoting M2 macrophage polarization in glioma.
Area of Science:
- Cell biology
- Cancer research
- Immunology
Background:
- Migrasomes are novel organelles involved in cell signaling and communication.
- TSPAN4 is a key regulator of migrasome formation, but its function in cancer is unknown.
Purpose of the Study:
- To investigate the role of TSPAN4 in various cancers.
- To explore the relationship between TSPAN4, tumor heterogeneity, stemness, and the tumor microenvironment.
- To examine TSPAN4's function in glioma, including its effect on cell proliferation and macrophage polarization.
Main Methods:
- Analysis of TCGA Pan-Cancer (PANCAN) and TCGA TARGET GTEx datasets for TSPAN4 expression and prognostic significance.
- Utilizing RNA-seq and scRNA-seq data to assess TSPAN4's correlation with tumor heterogeneity, stemness, and immune microenvironment.
- Investigating TSPAN4's impact on migrasome formation, cell proliferation, and macrophage polarization in glioma models.
Main Results:
- TSPAN4 is aberrantly expressed across multiple tumor types, potentially due to methylation.
- TSPAN4 expression correlates with increased tumor heterogeneity, stemness, and an immunosuppressive tumor microenvironment.
- In glioma, TSPAN4 promotes cell proliferation and M2 macrophage polarization, contributing to an immunosuppressive environment.
Conclusions:
- TSPAN4, a migrasome regulator, significantly influences the immunosuppressive tumor microenvironment in pan-cancer.
- TSPAN4 represents a potential therapeutic target for modulating the tumor microenvironment and improving cancer treatment outcomes.
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