Emerging roles of cystathionine β-synthase in various forms of cancer

Abstract

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 (H₂S) 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/H₂S 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.

Keywords: Angiogenesis; Colon cancer; Hydrogen sulfide; Mitochondria; Signalling; Stemness.