{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:00:27Z","timestamp":1790661627306,"version":"4.1.0"},"reference-count":90,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2025JJ50487"],"award-info":[{"award-number":["2025JJ50487"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2025JJ80840"],"award-info":[{"award-number":["2025JJ80840"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2025JJ80826"],"award-info":[{"award-number":["2025JJ80826"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Cyclin E1 (CCNE1), a pivotal member of the cyclin family, governs the G1\/S phase transition of the cell cycle by binding to and activating cyclin\u2010dependent kinase 2 (CDK2), thereby initiating DNA replication and driving S\u2010phase entry. In a broad spectrum of human malignancies\u2014including breast, ovarian, gastric, and non\u2010small cell lung cancers\u2014amplification or overexpression of CCNE1 disrupts the orderly regulation of cell cycle progression, leading to uncontrolled proliferation, impaired DNA damage repair, and genomic instability. These oncogenic consequences are intimately associated with increased tumor aggressiveness, poor patient prognosis, and diminished therapeutic efficacy. This review provides an integrated examination of CCNE1 biology, spanning its physiological regulation in the cell cycle, the molecular mechanisms by which its dysregulation drives tumorigenesis and drug resistance, the clinical implications of CCNE1 amplification as both a prognostic biomarker and a predictor of therapeutic response, and the emerging strategies to target CCNE1\u2010driven vulnerabilities. By synthesizing findings across diverse cancer types and regulatory layers, we evaluate the translational potential of CCNE1 as a diagnostic marker and therapeutic target, and highlight key challenges and opportunities for future investigation.<\/jats:p>","DOI":"10.1002\/cam4.72336","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:22:03Z","timestamp":1790659323000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>CCNE1<\/scp>\n                    : A Cell Cycle Regulator That Influences Tumor Progression"],"prefix":"10.1002","volume":"15","author":[{"given":"Liang","family":"Yan","sequence":"first","affiliation":[{"name":"Office of Scientific Research Administration, the Affiliated Cancer Hospital of Xiangya School of Medicine Central South University\/Hunan Cancer Hospital Changsha Hunan China"},{"name":"Cancer Research Institute, Basic School of Medicine, Central South University Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3175-2862","authenticated-orcid":false,"given":"Siyi","family":"Liu","sequence":"additional","affiliation":[{"name":"Cancer Research Institute, Basic School of Medicine, Central South University Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanling","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine The Affiliated Cancer Hospital of Xiangya School of Medicine Central South University\/Hunan Cancer Hospital Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"He","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology The Affiliated Cancer Hospital of Xiangya School of Medicine Central South University\/Hunan Cancer Hospital Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9613-4271","authenticated-orcid":false,"given":"Chen","family":"Long","sequence":"additional","affiliation":[{"name":"Department of General Surgery The Second Xiangya Hospital of Central South University Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Tang","sequence":"additional","affiliation":[{"name":"Office of Scientific Research Administration, the Affiliated Cancer Hospital of Xiangya School of Medicine Central South University\/Hunan Cancer Hospital Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9498-4439","authenticated-orcid":false,"given":"Yanhong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Cancer Research Institute, Basic School of Medicine, Central South University Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"issue":"5","key":"e_1_2_15_2_1","doi-asserted-by":"crossref","DOI":"10.3390\/diagnostics10050279","article-title":"CCNE1 Amplification as a Predictive Biomarker of Chemotherapy Resistance in Epithelial Ovarian Cancer","volume":"10","author":"Gorski J. W.","year":"2020","journal-title":"Diagnostics"},{"issue":"6","key":"e_1_2_15_3_1","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1016\/0092-8674(91)90042-W","article-title":"Isolation of Three Novel Human Cyclins by Rescue of G1 Cyclin (Cln) Function in Yeast","volume":"66","author":"Lew D. J.","year":"1991","journal-title":"Cell"},{"issue":"6","key":"e_1_2_15_4_1","first-page":"1173","article-title":"Regulation of Cyclin E Transcription by E2Fs and Retinoblastoma Protein","volume":"12","author":"Geng Y.","year":"1996","journal-title":"Oncogene"},{"issue":"6","key":"e_1_2_15_5_1","doi-asserted-by":"crossref","DOI":"10.1042\/BSR20190381","article-title":"Down\u2010Regulation of CCNE1 Expression Suppresses Cell Proliferation and Sensitizes Gastric Carcinoma Cells to Cisplatin","volume":"39","author":"Zhang C.","year":"2019","journal-title":"Bioscience Reports"},{"issue":"11","key":"e_1_2_15_6_1","doi-asserted-by":"crossref","first-page":"725","DOI":"10.5483\/BMBRep.2009.42.11.725","article-title":"Down\u2010Regulation of the Cyclin E1 Oncogene Expression by microRNA\u201016\u20101 Induces Cell Cycle Arrest in Human Cancer Cells","volume":"42","author":"Wang F.","year":"2009","journal-title":"BMB Reports"},{"issue":"1","key":"e_1_2_15_7_1","doi-asserted-by":"crossref","DOI":"10.1002\/jgm.3285","article-title":"Long Non\u2010Coding RNA MCF2L\u2010AS1 Promotes the Aggressiveness of Colorectal Cancer by Sponging miR\u2010874\u20103p and Thereby Up\u2010Regulating CCNE1","volume":"23","author":"Huang F. K.","year":"2021","journal-title":"Journal of Gene Medicine"},{"key":"e_1_2_15_8_1","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.omto.2021.07.007","article-title":"Knockdown of SENP1 Inhibits HIF\u20101\u03b1 SUMOylation and Suppresses Oncogenic CCNE1 in Wilms Tumor","volume":"23","author":"Zhu S.","year":"2021","journal-title":"Molecular Therapy \u2010 Oncolytics"},{"issue":"1","key":"e_1_2_15_9_1","doi-asserted-by":"crossref","first-page":"8701","DOI":"10.1038\/s41598-022-12669-5","article-title":"Clinical Characteristics and Outcomes of Phase I Cancer Patients With CCNE1 Amplification: MD Anderson Experiences","volume":"12","author":"Yao S.","year":"2022","journal-title":"Scientific Reports"},{"issue":"7","key":"e_1_2_15_10_1","doi-asserted-by":"crossref","first-page":"3260","DOI":"10.1073\/pnas.97.7.3260","article-title":"Expression Analysis With Oligonucleotide Microarrays Reveals That MYC Regulates Genes Involved in Growth, Cell Cycle, Signaling, and Adhesion","volume":"97","author":"Coller H. 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