Hydrogen sulfide (H2S), an endogenously produced gasotransmitter, is involved in various important physiological and disease conditions, including vasodilation, stimulation of cellular bioenergetics, anti-inflammation, and pro-angiogenesis. In cancer, aberrant up-regulation of H2S-producing enzymes is frequently observed in different cancer types. The recognition that tumor-derived H2S plays various roles during cancer development reveals opportunities to target H2S-mediated signaling pathways in cancer therapy.
H2S is synthesized endogenously by two enzymes responsible for metabolizing L-cysteine: cystathionine β-synthase (CBS) and cystathionine g-lyase (CTH). Recent studies have demonstrated that novel post-translational modifications (PTMs) were mediated by H2S through the formation of a persulfide (-SSH) bond on Cysteine, and this modification is called protein S-sulfhydration. S-sulfhydration coordinates with other post-translational protein modifications such as phosphorylation and nitrosylation to regulate multiple cellular functions. Several molecules have been identified to exist this modification, including glyceraldehyde 3-phosphate dehydrogenase (GAPDH), protein tyrosine phosphatase 1B (PTP1B), androgen receptor (AR), p65 subunit of NF-kB, and PTEN. Endogenous H2S promotes tumor growth through induction of angiogenesis, regulation of mitochondrial bioenergetics, acceleration of cell cycle progression, and anti-apoptosis. However, the underlying mechanisms of how H2S-mediated signaling affects tumor progression and metastasis remain unclear. Therefore, we aim to investigate the role of H2S during cancer development.
