前列腺癌
DU145型
癌症研究
转移
基因敲除
癌症
癌细胞
骨转移
肿瘤进展
胱硫醚γ裂解酶
胱硫醚β合酶
医学
生物
化学
内科学
半胱氨酸
酶
生物化学
细胞凋亡
LNCaP公司
作者
Yi Hsiang Wang,Jo Ting Huang,Wen Ling Chen,Rong Hsuan Wang,Ming Chien Kao,Yan Pan,Shih-Hsuan Chan,Kuo‐Wang Tsai,Hsing Jien Kung,Kai-Ti Lin,Lu Hai Wang
标识
DOI:10.15252/embr.201845986
摘要
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.
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