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Targeted USP22 deletion decreased ATGL expression and lipolysis, subsequently inhibiting EPI-mediated breast cancer lung metastasis. USP22 acts as a bona fide deubiquitinase for the\n            <jats:italic>Atgl<\/jats:italic>\n            gene transcription factor FOXO1, and EPI architects a lipolysis signaling pathway to stabilize USP22 through AKT-mediated phosphorylation. Notably, USP22 phosphorylation levels are positively associated with EPI and with downstream pathways involving both FOXO1 and ATGL in breast cancers. Pharmacological USP22 inhibition synergized with \u03b2-blockers in treating preclinical xenograft breast cancer models. This study reveals a molecular pathway behind EPI\u2019s tumor-promoting effects and provides a strong rationale for combining USP22 inhibition with \u03b2-blockers to treat aggressive breast cancer.\n          <\/jats:p>","DOI":"10.1126\/sciadv.ado1533","type":"journal-article","created":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T18:00:58Z","timestamp":1723831258000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":35,"title":["Epinephrine promotes breast cancer metastasis through a ubiquitin-specific peptidase 22\u2013mediated lipolysis circuit"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9806-9254","authenticated-orcid":true,"given":"Yuanzhang","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Dalian Medical University, Dalian 116044, 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