The lysine specific demethylase-1 (LSD1/KDM1A) regulates VEGF-A expression in prostate cancer

Vasundhra Kashyap1, Shafqat Ahmad, Emeli M Nilsson

  • 1Department of Pharmacology, Weill Cornell Medical College, New York, NY 10065, USA.

Molecular Oncology
|February 7, 2013
PubMed

Insights

Lysine specific demethylase-1 (LSD1) overexpression correlates with prostate cancer recurrence and increased VEGF-A. Inhibiting LSD1 reduces cancer cell proliferation, suggesting it as a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Recurrent prostate cancer presents a significant clinical challenge.
  • Lysine specific demethylase-1 (LSD1/KDM1A) is a key regulator of histone methylation, implicated in various cancers.
  • LSD1 functions as a transcriptional co-regulator and influences DNA methylation and p53 activity.

Purpose of the Study:

  • To investigate the expression of LSD1 and JMJD2A in human prostate cancer specimens.
  • To correlate LSD1 and JMJD2A expression with prostate cancer progression markers like VEGF-A and cyclin A1.
  • To explore the therapeutic potential of targeting LSD1 in prostate cancer.

Main Methods:

  • Expression analysis of LSD1 and JMJD2A in prostate cancer tissues.
  • Correlation studies between LSD1/JMJD2A expression and VEGF-A/cyclin A1 levels.
  • siRNA-mediated functional depletion of LSD1 in prostate cancer cells.
  • Pharmacological inhibition of LSD1 in androgen-dependent and independent cell lines.

Main Results:

  • Elevated LSD1 expression, but not JMJD2A, correlates with prostate cancer recurrence and increased VEGF-A.
  • Functional depletion of LSD1 reduces VEGF-A expression and blocks androgen-induced expression of VEGF-A, PSA, and Tmprss2.
  • Pharmacological inhibition of LSD1 inhibits proliferation in both androgen-dependent and independent prostate cancer cell lines.
  • A direct mechanistic link between LSD1 overexpression and pro-angiogenic pathway activation was established.

Conclusions:

  • LSD1 overexpression is linked to prostate cancer progression and angiogenesis.
  • Targeting LSD1 offers a promising therapeutic strategy for both hormone-dependent and independent prostate cancer.
  • LSD1 inhibition demonstrates efficacy in reducing prostate cancer cell proliferation.

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