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Pluripotent stem cell protein Sox2 confers sensitivity to LSD1 inhibition in cancer cells

Xiaoming Zhang1, Fei Lu, Jing Wang

  • 1College of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, Guangdong 518055, China.

Cell Reports
|October 22, 2013
PubMed

Insights

Gene amplification of Sox2 is common in squamous cell carcinomas. Targeting LSD1 (lysine-specific demethylase 1) histone demethylase selectively inhibits growth in Sox2-expressing cancers, suggesting it as a novel therapeutic target.

Area of Science:

  • Epigenetics
  • Cancer Biology
  • Molecular Oncology

Background:

  • Sox2 gene amplification occurs in various squamous cell carcinomas (SCCs).
  • Elevated expression of LSD1 (lysine-specific demethylase 1) is observed in Sox2-expressing lung SCCs.

Purpose of the Study:

  • To investigate the role of LSD1 in Sox2-expressing cancers.
  • To determine if LSD1 is a potential therapeutic target for SCCs.

Main Methods:

  • Assessed LSD1 expression in lung SCCs.
  • Utilized LSD1-specific inhibitors to evaluate cancer cell growth.
  • Analyzed changes in Sox2 expression, cell cycle, and histone methylation (H3K4, H3K9, H3K27) upon LSD1 inactivation.

Main Results:

  • LSD1 inhibitors selectively impaired the growth of Sox2-expressing lung SCCs.
  • Sox2 expression correlated with sensitivity to LSD1 inhibition across multiple cancer types.
  • LSD1 inactivation reduced Sox2 levels, induced G1 cell-cycle arrest, and promoted differentiation via epigenetic modulation.

Conclusions:

  • LSD1 is a key regulator of Sox2 expression and cancer cell proliferation.
  • LSD1 inhibition represents a promising targeted therapy strategy for Sox2-positive SCCs.

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