Scholarlink

<p>Large-scale metabolomic analyses of pan-cancer cell line panels have provided significant insights into the relationships between metabolism and cancer cell biology. Here, we took a pathway-centric approach by transforming targeted metabolomic data into ratios to study associations between reactant and product metabolites in a panel of cancer and non-cancer cell lines. We identified five clusters of cells from various tissue origins. Of these, cells in Cluster 4 had high ratios of TCA cycle metabolites relative to pyruvate, produced more lactate yet consumed less glucose and glutamine, and greater OXPHOS activity compared to Cluster 3 cells with low TCA cycle metabolite ratios. This was due to more glutamine cataplerotic efflux and not glycolysis in cells of Cluster 4. In silico analyses of loss-of-function and drug sensitivity screens showed that Cluster 4 cells were more susceptible to gene deletion and drug targeting of glutamine metabolism and OXPHOS than cells in Cluster 3. Our results highlight the potential of pathway-centric approaches to reveal new aspects of cellular metabolism from metabolomic data.</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

Pathway metabolite ratios reveal distinctive glutamine metabolism in a subset of proliferating cells

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年6月5日

查看全文
  • Nancy T Santiappillai,
  • Yue Cao,
  • Mariam F Hakeem-Sanni,
  • Jean Yang,
  • Lake-Ee Quek,
  • Andrew J Hoy

摘要

Large-scale metabolomic analyses of pan-cancer cell line panels have provided significant insights into the relationships between metabolism and cancer cell biology. Here, we took a pathway-centric approach by transforming targeted metabolomic data into ratios to study associations between reactant and product metabolites in a panel of cancer and non-cancer cell lines. We identified five clusters of cells from various tissue origins. Of these, cells in Cluster 4 had high ratios of TCA cycle metabolites relative to pyruvate, produced more lactate yet consumed less glucose and glutamine, and greater OXPHOS activity compared to Cluster 3 cells with low TCA cycle metabolite ratios. This was due to more glutamine cataplerotic efflux and not glycolysis in cells of Cluster 4. In silico analyses of loss-of-function and drug sensitivity screens showed that Cluster 4 cells were more susceptible to gene deletion and drug targeting of glutamine metabolism and OXPHOS than cells in Cluster 3. Our results highlight the potential of pathway-centric approaches to reveal new aspects of cellular metabolism from metabolomic data.