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

Yi Hsiang Wang, Jo Ting Huang, Wen Ling Chen, Rong Hsuan Wang, Ming Chien Kao, Yan Ru Pan, Shih Hsuan Chan, Kuo Wang Tsai, Hsing Jien Kung, Kai Ti Lin, Lu Hai Wang

Research output: Contribution to journalArticle

Abstract

Hydrogen sulfide (H2S), 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 H2S-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 H2S-mediated sulfhydration on cysteine-38 of the NF-κB p65 subunit, resulting in increased IL-1β expression and H2S-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 H2S promotes prostate cancer progression and metastasis through IL-1β/NF-κB signaling pathways.

Original languageEnglish
Article numbere45986
JournalEMBO Reports
Volume20
Issue number10
DOIs
Publication statusPublished - Oct 4 2019

Keywords

  • cystathionine gamma-lyase
  • hydrogen sulfide
  • IL-1beta
  • NF-kappaB
  • prostate cancer

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

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  • Cite this

    Wang, Y. H., Huang, J. T., Chen, W. L., Wang, R. H., Kao, M. C., Pan, Y. R., Chan, S. H., Tsai, K. W., Kung, H. J., Lin, K. T., & Wang, L. H. (2019). Dysregulation of cystathionine γ-lyase promotes prostate cancer progression and metastasis. EMBO Reports, 20(10), [e45986]. https://doi.org/10.15252/embr.201845986