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Signal-transducing adaptor protein 1 (STAP1) in microglia promotes the malignant progression of glioma

Xinyu Yang1,2,3,4,5, Chunxia Ji1,2,3,4,5, Ying Qi1,2,3,4,5

  • 1Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.

Journal of Neuro-Oncology
|July 18, 2023
PubMed
Abstract

Insights

Signal-transducing adaptor protein 1 (STAP1) in glioma-associated microglia correlates with higher tumor malignancy and worse prognosis. STAP1 may hinder immune cell function, suggesting it as a potential therapeutic target for glioma.

Area of Science:

  • Neuro-oncology
  • Immunology
  • Molecular Biology

Background:

  • Glioma, a malignant brain tumor, has a poor prognosis.
  • Glioma-associated microglia/macrophages (GAMs) are key players in glioma pathogenesis.
  • Signal-transducing adaptor protein 1 (STAP1) is implicated in tumorigenesis and immunity, but its role in GAMs is unexplored.

Purpose of the Study:

  • Investigate the role of STAP1 in glioma-associated microglia.
  • Determine the association between STAP1 expression and glioma malignancy and prognosis.

Main Methods:

  • Analysis of The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases for STAP1 mRNA levels and clinical parameters.
  • Expression analysis using RNA-sequencing, qRT-PCR, Western blotting, immunohistochemistry, and immunofluorescence.
  • In vitro studies using BV-2 cells to assess STAP1 overexpression effects on phagocytosis and ARG1 expression.
  • In vivo studies using orthotopic and subcutaneous glioma mouse models to monitor tumor growth.

Main Results:

  • STAP1 expression in glioma-associated microglia positively correlates with glioma grade and poor prognosis.
  • STAP1 may promote M2-like polarization by upregulating ARG1 and inhibiting microglial phagocytosis.
  • Increased ARG1 expression may involve the IL-6/STAT3 pathway, while impaired phagocytosis may relate to decreased cofilin and filopodia.

Conclusions:

  • STAP1 is significantly associated with glioma malignancy.
  • STAP1 represents a potential novel therapeutic target for glioma treatment.
Keywords:
GliomaMicrogliaPolarisationSTAP1

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