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Dependency of NELF-E-SLUG-KAT2B epigenetic axis in breast cancer carcinogenesis

Jieqiong Zhang1,2, Zhenhua Hu1, Hwa Hwa Chung1

  • 1Chromatin Dynamics and Disease Epigenetics Lab, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, Proteos, Singapore, 138673, Republic of Singapore.

Nature Communications
|April 28, 2023
PubMed

Insights

Loss of the Negative Elongation Factor (NELF) complex inhibits breast cancer progression by downregulating epithelial-mesenchymal transition (EMT) and stemness. This involves the NELF-E-SLUG-KAT2B epigenetic axis, impacting patient prognosis.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Cancer cells reprogram transcription for tumor progression and metastasis.
  • The Negative Elongation Factor (NELF) complex's role in breast cancer is not fully understood.

Purpose of the Study:

  • To investigate the role of the NELF complex in breast cancer development.
  • To elucidate the molecular mechanisms linking NELF to epithelial-mesenchymal transition (EMT) and cancer progression.

Main Methods:

  • Utilized cancer cell lines and patient-derived tumor organoids.
  • Employed quantitative multiplexed Rapid Immunoprecipitation Mass spectrometry of Endogenous proteins (qPLEX-RIME).
  • Conducted integrative transcriptomic and genomic analyses.

Main Results:

  • Loss of NELF inhibits breast cancer by downregulating EMT and stemness genes.
  • NELF-E interacts with the EMT transcription factor SLUG, and NELF loss impairs SLUG binding.
  • KAT2B (histone acetyltransferase) is identified as a key target of the NELF-E-SLUG complex.
  • Inactivation of KAT2B mimics NELF ablation effects on EMT markers.

Conclusions:

  • A novel NELF-E-SLUG-KAT2B epigenetic axis is crucial for breast cancer carcinogenesis.
  • Elevated NELF-E and KAT2B expression correlate with poorer patient prognosis, indicating clinical relevance.

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