Work

SMARCA4 deficiency in glioblastoma: Mitochondrial transfer from MSCs and the clinical dilemma in targeting the tumor microenvironment

Year: 2026

Type: article

Abstract: INTRODUCTION: SMARCA4, a pivotal transcription activator regulating chromatin structure, gene expression, and cellular energy metabolism, has well-documented roles in various cancers. However, its specific function in glioblastoma (GBM) pathogenesis remains underexplored. This study investigates the correlation between SMARCA4 expression and GBM progression, with a focus on the tumor microenvironment. MATERIALS AND METHODS: Single-cell RNA sequencing analyzed dynamic niche cell proportion shifts (e.g., mesenchymal stromal cells, MSCs) during GBM progression. SMARCA4 knockdown was executed in MSCs for in vitro functional evaluations, while an immunodeficient xenograft model was utilized to assess the impact of SMARCA4-deficient MSCs on in vivo GBM progression. Mechanistic studies focused on microtubule-dependent mitochondrial transfer in IDH mutant/wild-type tumors. RESULTS: SMARCA4 was identified as a critical MSC regulator. Its knockdown altered MSC/GBM cell behavior in vitro, accelerated in vivo GBM progression, and worsened outcomes. SMARCA4-deficient MSCs enhanced GBM growth via mitochondrial transfer, altering MSC proliferative phenotype but increasing mitochondrial metabolic capacity. DISCUSSION: Our findings highlight SMARCA4's critical role in regulating MSC function within the GBM microenvironment. Targeting SMARCA4-mediated mitochondrial transfer in MSCs may represent a novel therapeutic strategy for GBM.

Source: Neoplasia

DOI: 10.1016/j.neo.2026.101288

Authors: Fan Yang, Lin Chen, Yuchen Shi, Lude Wang, Minfeng Tong

Institutions: Zhejiang University, Jinhua University of Vocational Technology, Jinhua Central Hospital

Language: English

Topic: Glioma Diagnosis and Treatment

Subfield: Genetics

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,530