{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T14:58:06Z","timestamp":1772895486704,"version":"3.50.1"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":1187,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,6]]},"abstract":"\n \n \n Cyclin G1 deficiency is associated with reduced incidence of carcinogen-induced hepatocellular carcinoma (HCC), but its function in HCC progression remains obscure. We report a critical role of cyclin G1 in HCC metastasis. Elevated expression of cyclin G1 was detected in HCCs (60.6%), and its expression levels were even higher in portal vein tumor thrombus. Clinicopathological analysis revealed a close correlation of cyclin G1 expression with distant metastasis and poor prognosis of HCC. Forced expression of cyclin G1 promoted epithelial-mesenchymal transition (EMT) and metastasis of HCC cells<\/jats:bold>\n \n in vitro\n <\/jats:bold>\n and<\/jats:bold>\n \n in vivo\n <\/jats:bold>. Cyclin G1 overexpression enhanced Akt activation through interaction with p85 (regulatory subunit of phosphoinositide 3-kinase [PI3K]), which led to subsequent phosphorylation of glycogen synthase kinase-3\u03b2 (GSK-3\u03b2) and stabilization of Snail, a critical EMT mediator. These results suggest that elevated cyclin G1 facilitates HCC metastasis by promoting EMT via PI3K\/Akt\/GSK-3\u03b2\/Snail-dependent pathway. Consistently, we have observed a significant correlation between cyclin G1 expression and p-Akt levels in a cohort of HCC patients, and found that combination of these two parameters is a more powerful predictor of poor prognosis.<\/jats:bold>\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions:<\/jats:title>\n \n Cyclin G1 plays a pivotal role in HCC metastasis and may serve as a novel prognostic biomarker and therapeutic target.<\/jats:bold>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/hep.25596","type":"journal-article","created":{"date-parts":[[2012,1,23]],"date-time":"2012-01-23T11:43:05Z","timestamp":1327318985000},"page":"1787-1798","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":84,"title":["Cyclin G1\u2013mediated epithelial-mesenchymal transition via phosphoinositide 3-kinase\/Akt signaling facilitates liver cancer progression"],"prefix":"10.1097","volume":"55","author":[{"given":"Wen","family":"Wen","sequence":"first","affiliation":[]},{"given":"Jin","family":"Ding","sequence":"additional","affiliation":[]},{"given":"Wen","family":"Sun","sequence":"additional","affiliation":[]},{"given":"Jing","family":"Fu","sequence":"additional","affiliation":[]},{"given":"Yao","family":"Chen","sequence":"additional","affiliation":[]},{"given":"Kun","family":"Wu","sequence":"additional","affiliation":[]},{"given":"Beifang","family":"Ning","sequence":"additional","affiliation":[]},{"given":"Tao","family":"Han","sequence":"additional","affiliation":[]},{"given":"Lei","family":"Huang","sequence":"additional","affiliation":[]},{"given":"Cheng","family":"Chen","sequence":"additional","affiliation":[]},{"given":"Dong","family":"Xie","sequence":"additional","affiliation":[]},{"given":"Zhong","family":"Li","sequence":"additional","affiliation":[]},{"given":"Gensheng","family":"Feng","sequence":"additional","affiliation":[]},{"given":"Mengchao","family":"Wu","sequence":"additional","affiliation":[]},{"given":"Weifen","family":"Xie","sequence":"additional","affiliation":[]},{"given":"Hongyang","family":"Wang","sequence":"additional","affiliation":[]}],"member":"276","reference":[{"key":"R1-17-20241201","first-page":"2113","article-title":"Cyclin 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A retrospective clinical study of 150 cases.","volume":"24","author":"Giannelli","year":"2002","journal-title":"Hepatol Res"},{"key":"R26-17-20241201","doi-asserted-by":"crossref","first-page":"3626","DOI":"10.1172\/JCI39374","article-title":"The polycomb group protein Bmi1 represses the tumor suppressor PTEN and induces epithelialmesenchymal transition in human nasopharyngeal epithelial cells.","volume":"119","author":"Song","year":"2009","journal-title":"J Clin Invest"},{"key":"R27-17-20241201","doi-asserted-by":"crossref","first-page":"7455","DOI":"10.1038\/sj.onc.1209085","article-title":"Perturbations of the AKT signaling pathway in human cancer.","volume":"24","author":"Altomare","year":"2005","journal-title":"Oncogene"},{"key":"R28-17-20241201","doi-asserted-by":"crossref","first-page":"36803","DOI":"10.1074\/jbc.M005912200","article-title":"Phosphatidylinositol 3kinase function is required for transforming growth factor betamediated epithelial to mesenchymal transition and cell migration.","volume":"275","author":"Bakin","year":"2000","journal-title":"J Biol Chem"},{"key":"R29-17-20241201","first-page":"2172","article-title":"The protein kinase Akt induces epithelial mesenchymal transition and promotes enhanced motility and invasiveness of squamous cell carcinoma lines.","volume":"63","author":"Grille","year":"2003","journal-title":"Cancer Res"},{"key":"R30-17-20241201","doi-asserted-by":"crossref","first-page":"2922","DOI":"10.1158\/0008-5472.CAN-06-3598","article-title":"PRL3 downregulates PTEN expression and signals through PI3K to promote epithelialmesenchymal transition.","volume":"67","author":"Wang","year":"2007","journal-title":"Cancer Res"},{"key":"R31-17-20241201","doi-asserted-by":"crossref","first-page":"2639","DOI":"10.1101\/gad.1011002","article-title":"Deregulated G1cyclin expression induces genomic instability by preventing efficient preRC formation.","volume":"16","author":"Tanaka","year":"2002","journal-title":"Genes Dev"},{"key":"R32-17-20241201","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1038\/nrc822","article-title":"Epithelialmesenchymal transitions in tumour progression.","volume":"2","author":"Thiery","year":"2002","journal-title":"Nat Rev Cancer"},{"key":"R33-17-20241201","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1038\/35000025","article-title":"The transcription factor snail controls epithelialmesenchymal transitions by repressing Ecadherin expression.","volume":"2","author":"Cano","year":"2000","journal-title":"Nat Cell Biol"},{"key":"R34-17-20241201","doi-asserted-by":"crossref","first-page":"4549","DOI":"10.1158\/0008-5472.CAN-05-3850","article-title":"Exploring a new twist on tumor metastasis.","volume":"66","author":"Yang","year":"2006","journal-title":"Cancer Res"},{"key":"R35-17-20241201","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1038\/ncb1173","article-title":"Dual regulation of Snail by GSK3betamediated phosphorylation in control of epithelialmesenchymal transition.","volume":"6","author":"Zhou","year":"2004","journal-title":"Nat Cell Biol"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.25596","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-201206000-00017","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T14:01:57Z","timestamp":1733061717000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-201206000-00017"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,6]]},"references-count":34,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2012]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.25596","relation":{},"ISSN":["0270-9139"],"issn-type":[{"value":"0270-9139","type":"print"}],"subject":[],"published":{"date-parts":[[2012,6]]}}}