@article{f0727777aac64973b08e80b5c2012c2d,
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 Kung, {Hsing Jien} and Lin, {Kai Ti} and Wang, {Lu Hai}",
note = "Funding Information: We thank the Pathology Core Lab of the National Health Research Institutes for all of the H&E and IHC staining. Yi-Hsiang carried out his thesis research under the auspices of the Graduate Program of Biotechnology in Medicine, National Tsing Hua University and National Health Research Institutes. This work is financially supported by the ?Chinese Medicine Research Center, China Medical University? from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education(MOE) in Taiwan (CMRC-CHM-6), National Health Research Institutes (NHRI) (NHRI 06A1-MGPP09-014), Ministry of Health and Welfare, (MOHW103-TDU-M-221-123017), and Ministry of Science and Technology (MOST), Taiwan (MOST 104-2320-B-039-055-MY3, MOST 104-2320-B-039-054-MY3, MOST 106-2811-B-039-004, MOST 106-2314-B-007-007, MOST 107-2320-B-007-003-MY3, MOST 108-2314-B-007-003-MY3). Funding Information: We thank the Pathology Core Lab of the National Health Research Institutes for all of the H&E and IHC staining. Yi‐Hsiang carried out his thesis research under the auspices of the Graduate Program of Biotechnology in Medicine, National Tsing Hua University and National Health Research Institutes. This work is financially supported by the “Chinese Medicine Research Center, China Medical University” from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education(MOE) in Taiwan (CMRC‐CHM‐6), National Health Research Institutes (NHRI) (NHRI 06A1‐MGPP09‐014), Ministry of Health and Welfare, (MOHW103‐TDU‐M‐221‐123017), and Ministry of Science and Technology (MOST), Taiwan (MOST 104‐2320‐B‐039‐055‐MY3, MOST 104‐2320‐B‐039‐054‐MY3, MOST 106‐2811‐B‐039‐004, MOST 106‐2314‐B‐007‐007, MOST 107‐2320‐B‐007‐003‐MY3, MOST 108‐2314‐B‐007‐003‐MY3). ",
year = "2019",
month = oct,
day = "4",
doi = "10.15252/embr.201845986",
language = "English",
volume = "20",
journal = "EMBO Reports",
issn = "1469-221X",
publisher = "Nature Publishing Group",
number = "10",
}
