{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T07:02:04Z","timestamp":1784876524237,"version":"3.55.0"},"reference-count":48,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational Med"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Triple\u2010negative breast cancer (TNBC) remains a major clinical challenge because of its aggressive characteristics, limited targeted treatment options, and frequent chemoresistance. However, the molecular mechanisms governing protein stability that drive TNBC progression and therapeutic resistance remain incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>TMEM92 expression and clinical relevance were evaluated using public datasets, patient specimens, and TNBC cell models. Loss\u2010of\u2010function, rescue, xenograft, protein interaction, and ubiquitination assays were performed to determine the biological function and molecular mechanism of TMEM92 in TNBC progression and cisplatin response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      TMEM92 was prominently expressed in TNBC and correlated with poor prognosis. Functionally, depletion of TMEM92 suppressed TNBC cell proliferation, migration, invasion, and survival while promoting apoptosis in vitro and in vivo. Mechanistically, TMEM92 directly associated with DEAD\u2010box helicase 3 X\u2010linked (DDX3X) and protected it from degradation by the E3 ubiquitin ligase tetratricopeptide repeat domain 3 (TTC3). TMEM92 competitively prevented TTC3 binding to DDX3X, thereby inhibiting TTC3\u2010mediated K48\u2010linked ubiquitination and subsequent proteasomal degradation of DDX3X. Re\u2010expression of DDX3X rescued the anti\u2010tumor effects induced by TMEM92 knockdown. Therapeutically, TMEM92 targeting sensitized TNBC cells and xenograft tumors to cisplatin. TMEM92 knockout reduced the cisplatin IC\n                      <jats:sub>50<\/jats:sub>\n                      by 44.0% in MDA\u2010MB\u2010231 cells and 42.9% in BT\u2010549 cells, and TMEM92 depletion enhanced cisplatin\u2010induced tumor growth inhibition by approximately 70.6% compared with cisplatin alone.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study identifies a novel TMEM92DDX3XTTC3 axis that regulates DDX3X protein stability and drives TNBC progression and chemoresistance, revealing a potential prognostic and therapeutic vulnerability in TNBC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70681","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T13:10:17Z","timestamp":1778850617000},"source":"Crossref","is-referenced-by-count":0,"title":["TMEM92 shields DDX3X from TTC3\u2010mediated degradation to confer chemoresistance in triple\u2010negative breast cancer"],"prefix":"10.1002","volume":"16","author":[{"given":"Hao","family":"Shen","sequence":"first","affiliation":[{"name":"Department of Thyroid Breast Surgery Shanghai East Hospital, School of Medicine, Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaochao","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Medical Ultrasound Jinshan Hospital of Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Li","sequence":"additional","affiliation":[{"name":"Center of Hepatobiliary Pancreatic Disease Xuzhou Central Hospital  Xuzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Breast and Thyroid Surgery The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University  Huai'an Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medical Ultrasound Jinshan Hospital of Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Medical Ultrasound Jinshan Hospital of Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Thyroid Breast Surgery Shanghai East Hospital, School of Medicine, Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqiu","family":"Bu","sequence":"additional","affiliation":[{"name":"Department of Thyroid Breast Surgery Shanghai East Hospital, School of Medicine, Tongji University  Shanghai 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