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Monomethyltransferase SETD8 regulates breast cancer metabolism via stabilizing hypoxia-inducible factor 1α

Run Huang1, Yang Yu2, Xiangyun Zong1

  • 1Department of Breast Surgery, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China.

Cancer Letters
|January 17, 2017
PubMed

Insights

The study reveals SETD8 (SET Domain Containing 8) regulates anabolic metabolism in breast cancer by stabilizing hypoxia-inducible factor 1α (HIF1α). This highlights SETD8

Area of Science:

  • Epigenetics and Cancer Metabolism
  • Molecular Biology
  • Biochemistry

Background:

  • SETD8 (SET Domain Containing 8) is a histone methyltransferase regulating cell cycle and DNA repair.
  • Previous research linked SETD8 to epithelial-mesenchymal transition (EMT) and breast cancer metastasis.
  • The role of SETD8 in cancer metabolism reprogramming remained unexplored.

Purpose of the Study:

  • To investigate the role of SETD8 in metabolic reprogramming in breast cancer.
  • To elucidate the molecular mechanisms by which SETD8 influences cancer metabolism.
  • To explore the clinical relevance of SETD8 in breast cancer patients.

Main Methods:

  • Cell-based assays to assess metabolic changes.
  • Western blotting and qRT-PCR to analyze protein and gene expression.
  • Analysis of clinical breast cancer patient tissues.

Main Results:

  • SETD8 acts as a positive regulator of anabolic metabolism in breast cancer cells.
  • SETD8 reprograms metabolism via a hypoxia-inducible factor 1α (HIF1α)-dependent pathway.
  • SETD8 stabilizes HIF1α protein levels through post-transcriptional regulation and is a HIF1α target gene.
  • A positive correlation between SETD8, HIF1α, and HIF1α target genes was observed in clinical samples.

Conclusions:

  • SETD8 is identified as a novel regulator of metabolic reprogramming in breast cancer.
  • The SETD8-HIF1α axis plays a crucial role in maintaining breast cancer malignancy.
  • These findings offer new insights into the functions of SETD8 in cancer progression.
Keywords:
Breast cancerCancer metabolismGlycolysisHIF1αSETD8

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