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Human BLBC tumors exhibit elevated levels of cystathione \u03b2-synthetase (CBS) but diminished expressions of oxidative Cys-catabolizing enzymes supporting a Cys-addicted phenotype. We demonstrated that in BLBC cells, CBS plays a role in cellular proliferation and invasiveness, HIF1-\u03b1 activation under hypoxia, and protection against oxidative stress and CySSCy deprivation\u2013induced ferroptosis. Tumor progression and angiogenesis was impaired in shCBS xenograft tumors, which had larger intratumoral necrotic areas. Mechanistic analyses largely based on sulfur metabolome and proteomics data revealed that realigned Cys persulfidation is a determining factor in this Cys-addicted phenotype of BLBC tumors, which holds promise for drug development.<\/jats:p>","DOI":"10.1073\/pnas.2100050118","type":"journal-article","created":{"date-parts":[[2021,11,4]],"date-time":"2021-11-04T16:40:19Z","timestamp":1636044019000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":85,"title":["Reprogrammed transsulfuration promotes basal-like breast tumor progression via realigning cellular cysteine persulfidation"],"prefix":"10.1073","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8802-1292","authenticated-orcid":false,"given":"Katalin","family":"Erd\u00e9lyi","sequence":"first","affiliation":[{"name":"Department of Molecular Immunology and Toxicology, National Institute of Oncology, 1122 Budapest, 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