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Updated: Jan 12, 2026

Analysis of SCAP N-glycosylation and Trafficking in Human Cells
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RUNX2 cooperates with SREBP1 to rewire cancer metabolism and promote aggressiveness

Emanuele Vitale1,2, Mila Gugnoni1, Veronica Manicardi1

  • 1Laboratory of Translational Research, Azienda USL-IRCCS di Reggio Emilia, Viale Risorgimento 80, Reggio Emilia, 42124, Italy.

Journal of Experimental & Clinical Cancer Research : CR
|November 1, 2025
PubMed

Insights

Embryonic transcription factors (TFs) like RUNX2 reactivate in cancer, driving plasticity and metastasis. RUNX2 rewires cancer cell metabolism, repressing respiration and promoting lipid synthesis, which correlates with aggressive disease.

Area of Science:

  • Oncology
  • Molecular Biology
  • Metabolism

Background:

  • Embryonic transcription factors (TFs) are reactivated in cancers, promoting developmental gene programs and phenotypic plasticity.
  • Metabolic adaptation is crucial for cancer cell growth, providing energy and building blocks.
  • RUNX2, a bone morphogenetic TF, is ectopically expressed in epithelial cancers, driving metastasis via Epithelial-to-Mesenchymal Transition (EMT) and osteomimicry.

Purpose of the Study:

  • To investigate the role of RUNX2 in cancer cell metabolic rewiring.
  • To elucidate the mechanisms by which RUNX2 influences metabolic adaptation and promotes cancer progression.
  • To correlate RUNX2-driven metabolic changes with clinical aggressiveness and metastatic potential.

Main Methods:

  • Integration of omics data with functional validation experiments.
  • Analysis of RUNX2's regulatory effects on mitochondrial respiration and anabolic processes.
  • Investigation of RUNX2's interaction with SREBP1 in regulating lipid biosynthesis genes.
  • In vivo expression analysis in thyroid and breast cancer patient cohorts.

Main Results:

  • RUNX2 represses mitochondrial respiration while promoting anabolic processes in cancer cells.
  • RUNX2 upregulates key genes involved in lipid biosynthesis through regulation and cooperation with SREBP1.
  • Increased expression of lipid metabolism genes and SREBF1 correlates with higher metastatic potential and clinical aggressiveness in thyroid and breast cancers.

Conclusions:

  • RUNX2 plays a significant role in driving cancer cell plasticity by inducing metabolic rewiring.
  • Metabolic adaptation, particularly lipid biosynthesis, is an integral part of the trans-differentiation program induced by RUNX2.
  • Targeting RUNX2-mediated metabolic pathways may offer novel therapeutic strategies for aggressive epithelial cancers.
Keywords:
Cancer cell metabolic rewiringEmbryonic transcription factorsLipid biosynthesisOncogenic gene expression programs

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