Dysregulation of cystathionine γ-lyase promotes prostate cancer progression and metastasis

EMBO Rep. 2019 Oct 4;20(10):e45986. doi: 10.15252/embr.201845986. Epub 2019 Aug 29.


Hydrogen sulfide (H2 S), an endogenous signaling gaseous molecule, is involved in various physiological activities, including vessel relaxation, regulation of cellular bioenergetics, inflammation, and angiogenesis. By using xenograft orthotopic implantation of prostate cancer PC3 cells and subsequently comparing bone metastatic with primary tumor-derived cancer cells, we find that H2 S-producing enzyme cystathionine γ-lyase (CTH) is upregulated in bone-metastatic PC3 cells. Clinical data further reveal that the expression of CTH is elevated in late-stage prostate cancer patients, and higher CTH expression correlates with poor survival from The Cancer Genome Atlas (TCGA) prostate cancer RNA-seq datasets. CTH promotes NF-κB nuclear translocation through H2 S-mediated sulfhydration on cysteine-38 of the NF-κB p65 subunit, resulting in increased IL-1β expression and H2 S-induced cell invasion. Knockdown of CTH in PC3 cells results in the suppression of tumor growth and distant metastasis, while overexpression of CTH in DU145 cells promotes primary tumor growth and lymph node metastasis in the orthotopic implanted xenograft mouse model. Together, our findings provide evidence that CTH generated H2 S promotes prostate cancer progression and metastasis through IL-1β/NF-κB signaling pathways.

Keywords: IL-1beta; NF-kappaB; cystathionine gamma-lyase; hydrogen sulfide; prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Neoplasms / secondary
  • Cell Line, Tumor
  • Cell Movement
  • Cell Nucleus / metabolism
  • Cell Proliferation
  • Cystathionine gamma-Lyase / metabolism*
  • Disease Progression*
  • Gene Expression Regulation, Neoplastic
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Hydrogen Sulfide / metabolism
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Lymphatic Metastasis / pathology
  • Male
  • Mice, Nude
  • Models, Biological
  • NF-kappa B / metabolism
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Prostatic Neoplasms / enzymology*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / pathology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Signal Transduction
  • Survival Analysis
  • Up-Regulation / genetics
  • Xenograft Model Antitumor Assays


  • Interleukin-1beta
  • NF-kappa B
  • RNA, Messenger
  • Cystathionine gamma-Lyase
  • Hydrogen Sulfide