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Inhibiting SETD7 methyl-transferase activity impairs differentiation, lipid metabolism and lactogenesis in mammary

Fátima Liliana Monteiro1, André Góis1, Inês Direito1

  • 1Institute of Biomedicine (IBIMED), Department of Medical Sciences (DCM), Universidade de Aveiro, Portugal.

FEBS Letters
|September 18, 2023
PubMed

Insights

Inhibiting SETD7 (SET7/9, KMT7) catalytic activity impairs mammary epithelial and lactogenic differentiation. This study found that blocking SETD7 increases cell proliferation and disrupts key differentiation markers and lipid metabolism.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Background:

  • SETD7 (SET7/9, KMT7) is a lysine methyltransferase regulating cell proliferation and differentiation.
  • Understanding SETD7's role is crucial for mammary gland development and function.

Purpose of the Study:

  • To investigate the impact of inhibiting SETD7 catalytic activity on mammary epithelial cell differentiation.
  • To analyze the effects on genes involved in epithelial differentiation, lactogenesis, and lipid metabolism.

Main Methods:

  • Utilized HC11 and EpH4 cell lines to study mammary epithelial cell differentiation.
  • Inhibited SETD7 catalytic activity using the compound (R)-PFI-2.
  • Assessed changes in gene and protein expression, cell proliferation, and lipid profiles.

Main Results:

  • SETD7 mRNA and protein levels increased during lactogenic differentiation.
  • SETD7 inhibition led to increased cell proliferation and downregulation of key differentiation markers (e.g., E-cadherin, beta-casein).
  • Inhibition affected lipid profiles and altered expression of phospholipid biosynthesis genes.

Conclusions:

  • SETD7 catalytic activity is essential for proper mammary epithelial and lactogenic differentiation.
  • Inhibiting SETD7 disrupts critical pathways involved in cell differentiation and lipid metabolism.
Keywords:
epithelial differentiationlactogenesislipid metabolismmammary epithelial cells

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