Cysteine is a non-essential amino acid, because human cells can produce it via the transsulfuration pathways. However, some tumors are addicted to cysteine and heavily rely on its constant exogenous supply. In a number of cancers, the transsulfuration machinery is also realigned, which seems to serve different purposes in the progression of the disease in a tumor type specific manner.
We and others have demonstrated that characteristic changes in transsulfuration enzyme expression levels reprogram cysteine metabolism to produce cysteine-persulfide species in different pathways, which can support 1) tumor cell proliferation, 2) angiogenesis, 3) hypoxic response, 4) protection against oxidative stress and ferroptotic cell death, 5) metastasis formation and 6) development of resistance to therapeutic interventions. In this presentation I will reveal mechanistic details on how the utilization of cystine/cysteine via transsulfuration enzyme activities can support tumor progression in different cancer types.