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Updated: Jun 29, 2025
FIBS-enabled Noninvasive Metabolic Profiling
Published on: February 3, 2014
E2F transcription factor-1 modulates expression of glutamine metabolic genes in mouse embryonic fibroblasts and
Katharina Huber1, Albert Giralt2, René Dreos2
1Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland; Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
Abstract:
Metabolic reprogramming is considered as a hallmark of cancer and is clinically exploited as a novel target for therapy. The E2F transcription factor-1 (E2F1) regulates various cellular processes, including proliferative and metabolic pathways, and acts, depending on the cellular and molecular context, as an oncogene or tumor suppressor. The latter is evident by the observation that E2f1-knockout mice develop spontaneous tumors, including uterine sarcomas. This dual role warrants a detailed investigation of how E2F1 loss impacts metabolic pathways related to cancer progression. Our data indicate that E2F1 binds to the promoter of several glutamine metabolism-related genes. Interestingly, the expression of genes in the glutamine metabolic pathway were increased in mouse embryonic fibroblasts (MEFs) lacking E2F1. In addition, we confirm that E2f1-/- MEFs are more efficient in metabolizing glutamine and producing glutamine-derived precursors for proliferation. Mechanistically, we observe a co-occupancy of E2F1 and MYC on glutamine metabolic promoters, increased MYC binding after E2F1 depletion and that silencing of MYC decreased the expression of glutamine-related genes in E2f1-/- MEFs. Analyses of transcriptomic profiles in 29 different human cancers identified uterine sarcoma that showed a negative correlation between E2F1 and glutamine metabolic genes. CRISPR/Cas9 knockout of E2F1 in the uterine sarcoma cell line SK-UT-1 confirmed elevated glutamine metabolic gene expression, increased proliferation and increased MYC binding to glutamine-related promoters upon E2F1 loss. Together, our data suggest a crucial role of E2F1 in energy metabolism and metabolic adaptation in uterine sarcoma cells.
Insights
Loss of E2F1 transcription factor increases glutamine metabolism and proliferation in uterine sarcoma. This metabolic shift, driven by MYC, highlights E2F1
Area of Science:
- Oncology
- Cancer Metabolism
- Molecular Biology
Background:
- Metabolic reprogramming is a cancer hallmark and therapeutic target.
- E2F1 acts as an oncogene or tumor suppressor, influencing proliferation and metabolism.
- E2f1-knockout mice develop tumors, including uterine sarcomas, indicating a role in cancer progression.
Purpose of the Study:
- Investigate the impact of E2F1 loss on metabolic pathways in cancer.
- Elucidate the role of E2F1 in uterine sarcoma progression and metabolic adaptation.
Main Methods:
- Analysis of E2F1 binding to glutamine metabolism genes.
- Assessing glutamine metabolism and proliferation in E2f1-knockout mouse embryonic fibroblasts (MEFs).
- Investigating the interplay between E2F1, MYC, and glutamine metabolism genes using transcriptomic and CRISPR/Cas9 knockout approaches in human uterine sarcoma cell lines.
Main Results:
- E2F1 binds to promoters of glutamine metabolism genes.
- E2f1-knockout MEFs exhibit increased glutamine metabolism and proliferation.
- E2F1 loss leads to elevated MYC binding and expression of glutamine metabolism genes in uterine sarcoma cells.
- A negative correlation between E2F1 and glutamine metabolic genes was observed in human uterine sarcomas.
Conclusions:
- E2F1 plays a critical role in regulating energy metabolism and metabolic adaptation in uterine sarcoma.
- Loss of E2F1 promotes a metabolic shift towards glutamine utilization, enhancing proliferation.
- Targeting E2F1 or MYC-mediated glutamine metabolism may offer therapeutic strategies for uterine sarcoma.
