Scholarlink

<p>Glioblastoma is the most aggressive primary brain tumor in adults, with limited therapeutic success and, therefore, poor prognosis. Its malignancy is partly driven by the high proliferative capacity of glioblastoma cells, yet the underlying molecular mechanisms remain unclear. Recent studies have revealed transcriptomic similarities between glioblastoma cells and human fetal neural stem/progenitor cells (NSCs), suggesting that glioblastoma may exploit developmental programs that promote NSC proliferation. Fetal human NSCs rely on glutaminolysis—a metabolic pathway induced by the human-specific mitochondrial protein ARHGAP11B—to sustain proliferation. Here, we show that <i>ARHGAP11B</i> expression correlates with glioma malignancy and is essential for glioblastoma cell proliferation, implicating a critical role of glutaminolysis in tumor growth. Among glutaminolysis-related enzymes, glutamic-oxaloacetic transaminase 2 (<i>GOT2</i>) shows a strong positive correlation with glioma grade and poor patient prognosis. Functional assays reveal that GOT2 knockdown significantly suppresses glioblastoma cell growth, indicating that GOT2-mediated glutaminolysis is critical for their proliferation. Metabolomic profiling further shows that GOT2 is required for nucleotide precursor synthesis, underscoring its role in supporting DNA replication. Consistently, GOT2 depletion reduces the proportion of glioblastoma cells in the S phase of the cell cycle. These findings suggest glioblastoma cells hijack an evolutionarily adapted metabolic program to support malignant growth.</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

Glioblastoma cells utilize evolutionarily adapted cell metabolism to promote their malignant proliferation

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月13日

查看全文
  • Maxim M. Bespalov,
  • Vasiliki Gkini,
  • Zeynep Iloglu,
  • Seiya Yamada,
  • Akira Nemoto,
  • Pauliina Filppu,
  • Kalevi Trontti,
  • Liliia Andriichuk,
  • Olli Pietiläinen,
  • Vadim Le Joncour,
  • Anni I. Nieminen,
  • Pirjo Laakkonen,
  • Takashi Namba

摘要

Glioblastoma is the most aggressive primary brain tumor in adults, with limited therapeutic success and, therefore, poor prognosis. Its malignancy is partly driven by the high proliferative capacity of glioblastoma cells, yet the underlying molecular mechanisms remain unclear. Recent studies have revealed transcriptomic similarities between glioblastoma cells and human fetal neural stem/progenitor cells (NSCs), suggesting that glioblastoma may exploit developmental programs that promote NSC proliferation. Fetal human NSCs rely on glutaminolysis—a metabolic pathway induced by the human-specific mitochondrial protein ARHGAP11B—to sustain proliferation. Here, we show that ARHGAP11B expression correlates with glioma malignancy and is essential for glioblastoma cell proliferation, implicating a critical role of glutaminolysis in tumor growth. Among glutaminolysis-related enzymes, glutamic-oxaloacetic transaminase 2 (GOT2) shows a strong positive correlation with glioma grade and poor patient prognosis. Functional assays reveal that GOT2 knockdown significantly suppresses glioblastoma cell growth, indicating that GOT2-mediated glutaminolysis is critical for their proliferation. Metabolomic profiling further shows that GOT2 is required for nucleotide precursor synthesis, underscoring its role in supporting DNA replication. Consistently, GOT2 depletion reduces the proportion of glioblastoma cells in the S phase of the cell cycle. These findings suggest glioblastoma cells hijack an evolutionarily adapted metabolic program to support malignant growth.