{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T15:59:24Z","timestamp":1791993564447,"version":"4.4.0"},"reference-count":41,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T00:00:00Z","timestamp":1643932800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cytoplasmic chromatin fragments (CCF) are recognized by the cytoplasmic DNA sensor cyclic GMP-AMP synthase (cGAS), which activates the cGAS\u2013STING (cyclic GMP-AMP synthase-stimulator of interferon genes) pathway and promotes the production of inflammatory factors and breast cancer metastasis. However, the mechanisms by which CCF are formed in tumor cells and CCF activation cGAS promotes breast cancer metastasis remain unclear. Here, we report that the enhancer of zeste homolog 2 (EZH2) can promote the formation of CCF and activate the cGAS\u2013STING pathway to promote breast cancer metastasis. Further research found that the EZH2-mediated CCF formation depended on high mobility group A1 (HMGA1), while the stability of EZH2 required ubiquitin-specific peptidase 7 (USP7), indicating that the EZH2\u2013HMGA1\u2013USP7 complex regulated CCF formation. Moreover, EZH2 can activate cGAS through CCF, requiring USP7 to deubiquitinate cGAS and stabilize cGAS. In vivo experimental results showed that EZH2 could promote breast cancer metastasis through CCF. Our findings highlight a new target for breast cancer metastasis. Targeting the EZH2\u2013CCF\u2013cGAS axis may be a potential therapeutic strategy for inhibiting breast cancer metastasis.<\/jats:p>","DOI":"10.3390\/ijms23031788","type":"journal-article","created":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T11:35:17Z","timestamp":1643974517000},"page":"1788","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["EZH2\u2013CCF\u2013cGAS Axis Promotes Breast Cancer Metastasis"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5145-9864","authenticated-orcid":false,"given":"Dandan","family":"Duan","sequence":"first","affiliation":[{"name":"The Key Laboratory of Molecular Epigenetics of Ministry of Education (MOE), Northeast Normal University, Changchun 130024, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengjie","family":"Shang","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Molecular Epigenetics of Ministry of Education (MOE), Northeast Normal University, Changchun 130024, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanxu","family":"Han","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Molecular Epigenetics of Ministry of Education (MOE), Northeast Normal University, Changchun 130024, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayuan","family":"Liu","sequence":"additional","affiliation":[{"name":"The Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiwei","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Life Science and Technology, Inner Mongolia University of Science & Technology, Baotou 014010, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun Hyok","family":"Kong","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Molecular Epigenetics of Ministry of Education (MOE), Northeast Normal University, Changchun 130024, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyao","family":"Hou","sequence":"additional","affiliation":[{"name":"The Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baiqu","family":"Huang","sequence":"additional","affiliation":[{"name":"The Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Lu","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Molecular Epigenetics of Ministry of Education (MOE), Northeast Normal University, Changchun 130024, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3702-6541","authenticated-orcid":false,"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Molecular Epigenetics of Ministry of Education (MOE), Northeast Normal University, Changchun 130024, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1038\/sj.embor.7400839","article-title":"Mammary gland biology and breast cancer. 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