Molecular Functions of Hydrogen Sulfide in Cancer

Hydrogen sulfide (H(2)S) is a gasotransmitter that exerts a multitude of functions in both physiologic and pathophysiologic processes. H(2)S-synthesizing enzymes are increased in a variety of human malignancies, including colon, prostate, breast, renal, urothelial, ovarian, oral squamous cell, and thyroid cancers. In cancer, H(2)S promotes tumor growth, cellular and mitochondrial bioenergetics, migration, invasion, angiogenesis, tumor blood flow, metastasis, epithelia–mesenchymal transition, DNA repair, protein sulfhydration, and chemotherapy resistance Additionally, in some malignancies, increased H(2)S-synthesizing enzyme expression correlates with a worse prognosis and a higher tumor stage. Here we review the role of H(2)S in cancer, with an emphasis on the molecular mechanisms by which H(2)S promotes cancer development, progression, dedifferentiation, and metastasis.