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Glutamine withdrawal leads to the preferential activation of lipid metabolism in metastatic colorectal cancer

  • 0Department of Biological Sciences, Orta Doğu Teknik Üniversitesi, Ankara, Türkiye; Department of Molecular Biology and Genetics, Başkent University, Ankara, Türkiye.
Translational Oncology +

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August 7, 2024

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August 7, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Metastatic colorectal cancer (CRC) cells exhibit altered glutamine metabolism. These cells demonstrate metabolic plasticity, utilizing lipids for survival and motility when glutamine is unavailable.

Area Of Science

  • Oncology
  • Cancer Metabolism
  • Molecular Biology

Background

  • Glutamine is vital for cell growth, but its differential metabolism in metastatic versus primary colorectal cancer (CRC) remains under-explored.
  • Understanding these metabolic differences is crucial for developing targeted therapies.

Purpose Of The Study

  • To investigate the differential metabolism of L-glutamine in primary and metastatic colorectal cancer (CRC) cells.
  • To identify metabolic pathways and gene signatures associated with CRC metastasis and prognosis.

Main Methods

  • Comparative analysis of glutamine-related gene expression in primary and metastatic CRC.
  • Utilized univariate Cox regression and hierarchical clustering for gene signature development.
  • Employed untargeted metabolomics and 18O-based fluxomics on paired SW480 (primary) and SW620 (metastatic) CRC cells.

Main Results

  • "Glutamine metabolism" gene ontology term significantly enriched in metastatic CRC.
  • Metastatic SW620 cells showed decreased E-cadherin and increased motility upon L-glutamine withdrawal.
  • Identified and validated a prognostic gene signature related to glutamine metabolism.
  • SW620 cells maintained high ATP levels by metabolizing lipids, unlike SW480 cells, upon L-glutamine withdrawal.

Conclusions

  • Metastatic CRC cells display aberrant glutamine metabolism and significant metabolic plasticity.
  • SW620 cells preferentially metabolize lipids from the environment for survival and motility when L-glutamine is withdrawn.
  • Findings highlight potential therapeutic targets in the metabolic pathways of metastatic CRC.

Keywords: