Lysine-specific demethylase 1 controls key OSCC preneoplasia inducer STAT3 through CDK7 phosphorylation during oncogenic progression and immunosuppression.

ABSTRACT: Oral squamous cell carcinoma (OSCC) progresses from preneoplastic precursors via genetic and epigenetic alterations. Previous studies have focused on the treatment of terminally developed OSCC. However, the role of epigenetic regulators as therapeutic targets during the transition from preneoplastic precursors to OSCC has not been well studied. Our study identified lysine-specific demethylase 1 (LSD1) as a crucial promoter of OSCC, demonstrating that its knockout or pharmacological inhibition in mice reversed OSCC preneoplasia. LSD1 inhibition by SP2509 disrupted cell cycle, reduced immunosuppression, and enhanced CD4+ and CD8+ T-cell infiltration. In a feline model of spontaneous OSCC, a clinical LSD1 inhibitor (Seclidemstat or SP2577) was found to be safe and effectively inhibit the STAT

SUBMITTER: Chakraborty AK 

PROVIDER: S-EPMC12006301 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature