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Updated: May 11, 2025

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Lysine-specific demethylase 1 controls key OSCC preneoplasia inducer STAT3 through CDK7 phosphorylation during

Amit Kumar Chakraborty1, Rajnikant Dilip Raut1, Kisa Iqbal1,2

  • 1Department of Translational Dental Medicine, Boston University Henry M. Goldman School of Dental Medicine, Boston, USA.

International Journal of Oral Science
|April 17, 2025
PubMed

Insights

Lysine-specific demethylase 1 (LSD1) promotes oral squamous cell carcinoma (OSCC) progression. Inhibiting LSD1 reversed preneoplasia, reduced immunosuppression, and enhanced T-cell infiltration in OSCC models.

Area of Science:

  • Oncology
  • Epigenetics
  • Cancer Biology

Background:

  • Oral squamous cell carcinoma (OSCC) develops through genetic and epigenetic changes.
  • Focus has been on treating advanced OSCC, neglecting epigenetic regulators in early stages.
  • The role of epigenetic regulators in OSCC preneoplasia remains understudied.

Purpose of the Study:

  • To investigate the role of lysine-specific demethylase 1 (LSD1) in OSCC progression.
  • To evaluate LSD1 as a therapeutic target for OSCC preneoplasia.
  • To elucidate the mechanisms by which LSD1 influences OSCC development.

Main Methods:

  • Genetic knockout and pharmacological inhibition of LSD1 in mouse models.
  • Assessment of cell cycle, immunosuppression, and T-cell infiltration.
  • Utilized a feline model of spontaneous OSCC with a clinical LSD1 inhibitor (Seclidemstat).
  • Investigated LSD1's effect on STAT3 signaling, CDK7, and CTLA4 phosphorylation.

Main Results:

  • LSD1 knockout or inhibition reversed OSCC preneoplasia in mice.
  • LSD1 inhibition disrupted the cell cycle, reduced immunosuppression, and increased T-cell infiltration.
  • Seclidemstat was safe and inhibited the STAT3 network in a feline OSCC model.
  • LSD1 inhibition reduced CDK7 and eIF4B phosphorylation, revealing a novel regulatory mechanism.

Conclusions:

  • LSD1 is a critical promoter of OSCC progression from preneoplastic lesions.
  • Targeting LSD1 offers a potential therapeutic strategy for early-stage OSCC.
  • LSD1 inhibition impacts key signaling pathways involved in cancer development and immune evasion.

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