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.

Frontiers in Immunology
|December 26, 2024
PubMed
Abstract

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.

Related Concept Videos

The Tumor Microenvironment02:17

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
6.4K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.3K
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
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...
4.6K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.6K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
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...
7.2K