title: Cyclin G1-mediated epithelial-mesenchymal transition via phosphoinositide 3-kinase/Akt signaling facilitates liver cancer progression.
abstract: 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 in vitro and in vivo. 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-3β (GSK-3β) 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-3β/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.
  
  
  CONCLUSIONS
  Cyclin G1 plays a pivotal role in HCC metastasis and may serve as a novel prognostic biomarker and therapeutic target.
authors.affiliation: International Cooperation Laboratory on Signal Transduction of Eastern Hepatobiliary Surgery Institute, Shanghai, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Wen
authors.forename: Jin
authors.initials: J
authors.lastname: Ding
authors.forename: Wen
authors.initials: W
authors.lastname: Sun
authors.forename: Jing
authors.initials: J
authors.lastname: Fu
authors.forename: Yao
authors.initials: Y
authors.lastname: Chen
authors.forename: Kun
authors.initials: K
authors.lastname: Wu
authors.forename: Beifang
authors.initials: B
authors.lastname: Ning
authors.forename: Tao
authors.initials: T
authors.lastname: Han
authors.forename: Lei
authors.initials: L
authors.lastname: Huang
authors.forename: Cheng
authors.initials: C
authors.lastname: Chen
authors.forename: Dong
authors.initials: D
authors.lastname: Xie
authors.forename: Zhong
authors.initials: Z
authors.lastname: Li
authors.forename: Gensheng
authors.initials: G
authors.lastname: Feng
authors.forename: Mengchao
authors.initials: M
authors.lastname: Wu
authors.forename: Weifen
authors.initials: W
authors.lastname: Xie
authors.forename: Hongyang
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000473:pathology* / Q000556:secondary; D056766:Cyclin G1 / Q000502:physiology*; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D038362:Glycogen Synthase Kinase 3 / Q000502:physiology; D000071679:Glycogen Synthase Kinase 3 beta; D008113:Liver Neoplasms / Q000209:etiology / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D056766:Cyclin G1; D019869:Phosphatidylinositol 3-Kinases; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3