Chair of Pharmacology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland.
Chair of Pharmacology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland.
Redox Biol. 2022 Jul;53:102331. doi: 10.1016/j.redox.2022.102331. Epub 2022 May 10.
The expression of the reverse transsulfuration enzyme cystathionine-β-synthase (CBS) is markedly increased in many forms of cancer, including colorectal, ovarian, lung, breast and kidney, while in other cancers (liver cancer and glioma) it becomes downregulated. According to the clinical database data in high-CBS-expressor cancers (e.g. colon or ovarian cancer), high CBS expression typically predicts lower survival, while in the low-CBS-expressor cancers (e.g. liver cancer), low CBS expression is associated with lower survival. In the high-CBS expressing tumor cells, CBS, and its product hydrogen sulfide (HS) serves as a bioenergetic, proliferative, cytoprotective and stemness factor; it also supports angiogenesis and epithelial-to-mesenchymal transition in the cancer microenvironment. The current article reviews the various tumor-cell-supporting roles of the CBS/HS axis in high-CBS expressor cancers and overviews the anticancer effects of CBS silencing and pharmacological CBS inhibition in various cancer models in vitro and in vivo; it also outlines potential approaches for biomarker identification, to support future targeted cancer therapies based on pharmacological CBS inhibition.
逆硫化酶胱硫醚-β-合酶（CBS）的表达在许多形式的癌症中明显增加，包括结直肠癌、卵巢癌、肺癌、乳腺癌和肾癌，而在其他癌症（肝癌和神经胶质瘤）中则下调。根据高 CBS 表达癌症（例如结肠癌或卵巢癌）的临床数据库数据，高 CBS 表达通常预示着较低的生存率，而在低 CBS 表达癌症（例如肝癌）中，低 CBS 表达与较低的生存率相关。在高 CBS 表达的肿瘤细胞中，CBS 及其产物硫化氢（HS）作为一种生物能量、增殖、细胞保护和干细胞因子；它还支持癌症微环境中的血管生成和上皮-间充质转化。本文综述了 CBS/HS 轴在高 CBS 表达癌症中对肿瘤细胞的各种支持作用，并概述了 CBS 沉默和药理学 CBS 抑制在各种体外和体内癌症模型中的抗癌作用；它还概述了用于鉴定生物标志物的潜在方法，以支持基于药理学 CBS 抑制的未来靶向癌症治疗。
