Scholarlink

Background <p>Brain metastasis (BrM) poses a significant challenge to the prognosis and quality of life for patients with non-small cell lung cancer (NSCLC). Gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in the central nervous system (CNS), has been implicated in the progression of various tumors. However, its potential role in BrM of NSCLC and the underlying mechanisms remain largely unexplored.</p> Methods <p>A multi-omics approach combined with in vivo and in vitro experiments identified GABA as a key target in BrM of NSCLC. Functional and mechanistic studies were conducted to investigate how GABA mediates brain metastasis through the activation of the NF-κB pathway.</p> Results <p>GABA levels were significantly elevated in both cells and serum of patients with NSCLC who had BrM. GABA markedly enhanced the brain metastatic capabilities and malignancy of NSCLC cells. Mechanistically, tumor cells with a tendency for brain metastasis can inhibit 4-aminobutyrate aminotransferase (ABAT) by downregulating forkhead box A2 (FOXA2) expression, leading to increased GABA accumulation. GABA subsequently activates the NF-κB pathway and the astrocytes, thus facilitating the brain metastasis of NSCLC.</p> Conclusions <p>Our findings indicate that GABA plays a crucial role in the development of NSCLC brain metastasis by activating the NF-κB pathway through the FOXA2/ABAT/GABA axis. Additionally, the interaction between NSCLC and astrocytes creates an inhibitory microenvironment that promotes tumor colonization.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

GABA regulates metabolic reprogramming to mediate the development of brain metastasis in non-small cell lung cancer

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年2月19日

查看全文
  • Mengqing Xie,
  • Hao Qin,
  • Li Liu,
  • Jing Wu,
  • Zhikai Zhao,
  • Yaodong Zhao,
  • Yujia Fang,
  • Xin Yu,
  • Chunxia Su

摘要

Background

Brain metastasis (BrM) poses a significant challenge to the prognosis and quality of life for patients with non-small cell lung cancer (NSCLC). Gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in the central nervous system (CNS), has been implicated in the progression of various tumors. However, its potential role in BrM of NSCLC and the underlying mechanisms remain largely unexplored.

Methods

A multi-omics approach combined with in vivo and in vitro experiments identified GABA as a key target in BrM of NSCLC. Functional and mechanistic studies were conducted to investigate how GABA mediates brain metastasis through the activation of the NF-κB pathway.

Results

GABA levels were significantly elevated in both cells and serum of patients with NSCLC who had BrM. GABA markedly enhanced the brain metastatic capabilities and malignancy of NSCLC cells. Mechanistically, tumor cells with a tendency for brain metastasis can inhibit 4-aminobutyrate aminotransferase (ABAT) by downregulating forkhead box A2 (FOXA2) expression, leading to increased GABA accumulation. GABA subsequently activates the NF-κB pathway and the astrocytes, thus facilitating the brain metastasis of NSCLC.

Conclusions

Our findings indicate that GABA plays a crucial role in the development of NSCLC brain metastasis by activating the NF-κB pathway through the FOXA2/ABAT/GABA axis. Additionally, the interaction between NSCLC and astrocytes creates an inhibitory microenvironment that promotes tumor colonization.