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 (US)
Article numbere45986
JournalEMBO Reports
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Cystathionine
Lyases
Prostatic Neoplasms
Neoplasm Metastasis
Tumors
Neoplasms
Interleukin-1
Heterografts
Bone
Bone and Bones
Hydrogen Sulfide
Atlases
Growth
Energy Metabolism
Cysteine
Genes
Lymph Nodes
Cells
Genome
RNA

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Wang, Y. H., Huang, J. T., Chen, W. L., Wang, R. H., Kao, M. C., Pan, Y. R., ... Wang, L. H. (Accepted/In press). Dysregulation of cystathionine γ-lyase promotes prostate cancer progression and metastasis. EMBO Reports, [e45986]. https://doi.org/10.15252/embr.201845986

Dysregulation of cystathionine γ-lyase promotes prostate cancer progression and metastasis. / Wang, Yi Hsiang; Huang, Jo Ting; Chen, Wen Ling; Wang, Rong Hsuan; Kao, Ming Chien; Pan, Yan Ru; Chan, Shih Hsuan; Tsai, Kuo Wang; Kung, Hsing-Jien; Lin, Kai Ti; Wang, Lu Hai.

In: EMBO Reports, 01.01.2019.

Research output: Contribution to journalArticle

Wang, YH, Huang, JT, Chen, WL, Wang, RH, Kao, MC, Pan, YR, Chan, SH, Tsai, KW, Kung, H-J, Lin, KT & Wang, LH 2019, 'Dysregulation of cystathionine γ-lyase promotes prostate cancer progression and metastasis', EMBO Reports. https://doi.org/10.15252/embr.201845986
Wang, Yi Hsiang ; Huang, Jo Ting ; Chen, Wen Ling ; Wang, Rong Hsuan ; Kao, Ming Chien ; Pan, Yan Ru ; Chan, Shih Hsuan ; Tsai, Kuo Wang ; Kung, Hsing-Jien ; Lin, Kai Ti ; Wang, Lu Hai. / Dysregulation of cystathionine γ-lyase promotes prostate cancer progression and metastasis. In: EMBO Reports. 2019.
@article{057795243d244952a7cf26712c49bff6,
title = "Dysregulation of cystathionine γ-lyase promotes prostate cancer progression and metastasis",
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.",
keywords = "cystathionine gamma-lyase, hydrogen sulfide, IL-1beta, NF-kappaB, prostate cancer",
author = "Wang, {Yi Hsiang} and Huang, {Jo Ting} and Chen, {Wen Ling} and Wang, {Rong Hsuan} and Kao, {Ming Chien} and Pan, {Yan Ru} and Chan, {Shih Hsuan} and Tsai, {Kuo Wang} and Hsing-Jien Kung and Lin, {Kai Ti} and Wang, {Lu Hai}",
year = "2019",
month = "1",
day = "1",
doi = "10.15252/embr.201845986",
language = "English (US)",
journal = "EMBO Reports",
issn = "1469-221X",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Dysregulation of cystathionine γ-lyase promotes prostate cancer progression and metastasis

AU - Wang, Yi Hsiang

AU - Huang, Jo Ting

AU - Chen, Wen Ling

AU - Wang, Rong Hsuan

AU - Kao, Ming Chien

AU - Pan, Yan Ru

AU - Chan, Shih Hsuan

AU - Tsai, Kuo Wang

AU - Kung, Hsing-Jien

AU - Lin, Kai Ti

AU - Wang, Lu Hai

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - cystathionine gamma-lyase

KW - hydrogen sulfide

KW - IL-1beta

KW - NF-kappaB

KW - prostate cancer

UR - http://www.scopus.com/inward/record.url?scp=85071369713&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85071369713&partnerID=8YFLogxK

U2 - 10.15252/embr.201845986

DO - 10.15252/embr.201845986

M3 - Article

AN - SCOPUS:85071369713

JO - EMBO Reports

JF - EMBO Reports

SN - 1469-221X

M1 - e45986

ER -