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P.N. acknowledges the Japan Society for the Promotion of Science (Invitational Fellowship L19520). M.K., O.C., and P.N. acknowledge financial support from the NVKP_16-1-2016-0005 from the Hungarian National Research, Development and Innovation Office. J.L. is supported by financing from the European Union's Horizon 2020 Research and Innovation Programme for the RESCUER project under Grant Agreement No. 847912, the Swedish Research Council, the Swedish Cancer Society, the Swedish Foundation for Strategic Research, and the Stockholm County Council; J.L. and H.J.J. are supported by the Cancer Society in Stockholm. 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Impaired Tyr phosphorylation was detected in shCBS cells and xenografts, likely due to persulfidation-inhibited phosphatase functions. Overexpression of cystathione γ-lyase (CSE), which can also contribute to cellular sulfide/persulfide production, compensated for the loss of CBS activities, and treatment of shCBS xenografts with a CSE inhibitor further blocked tumor growth. Glutathione and protein-Cys levels were not diminished in shCBS cells or xenografts, but levels of Cys persulfidation and the persulfide-catabolizing enzyme ETHE1 were suppressed. Finally, expression of enzymes of the oxidizing Cys catabolism pathway was diminished, but expression of the persulfide-producing CARS2 was elevated in human BLBC tumors. 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