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

Hydrogen sulfide (H(2)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 subseque...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776913/
https://www.ncbi.nlm.nih.gov/pubmed/31468690
http://dx.doi.org/10.15252/embr.201845986
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author 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
author_facet 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
author_sort Wang, Yi‐Hsiang
collection PubMed
description Hydrogen sulfide (H(2)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 H(2)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 H(2)S‐mediated sulfhydration on cysteine‐38 of the NF‐κB p65 subunit, resulting in increased IL‐1β expression and H(2)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 H(2)S promotes prostate cancer progression and metastasis through IL‐1β/NF‐κB signaling pathways.
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spelling pubmed-67769132019-10-07 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 EMBO Rep Articles Hydrogen sulfide (H(2)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 H(2)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 H(2)S‐mediated sulfhydration on cysteine‐38 of the NF‐κB p65 subunit, resulting in increased IL‐1β expression and H(2)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 H(2)S promotes prostate cancer progression and metastasis through IL‐1β/NF‐κB signaling pathways. John Wiley and Sons Inc. 2019-08-29 2019-10-04 /pmc/articles/PMC6776913/ /pubmed/31468690 http://dx.doi.org/10.15252/embr.201845986 Text en © 2019 The Authors. Published under the terms of the CC BY 4.0 license This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Articles
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
title Dysregulation of cystathionine γ‐lyase promotes prostate cancer progression and metastasis
title_full Dysregulation of cystathionine γ‐lyase promotes prostate cancer progression and metastasis
title_fullStr Dysregulation of cystathionine γ‐lyase promotes prostate cancer progression and metastasis
title_full_unstemmed Dysregulation of cystathionine γ‐lyase promotes prostate cancer progression and metastasis
title_short Dysregulation of cystathionine γ‐lyase promotes prostate cancer progression and metastasis
title_sort dysregulation of cystathionine γ‐lyase promotes prostate cancer progression and metastasis
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776913/
https://www.ncbi.nlm.nih.gov/pubmed/31468690
http://dx.doi.org/10.15252/embr.201845986
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