International Cooperation Laboratory on Signal Transduction of Eastern Hepatobiliary Surgery Institute

Shanghai, China

International Cooperation Laboratory on Signal Transduction of Eastern Hepatobiliary Surgery Institute

Shanghai, China
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Wen W.,International Cooperation Laboratory on Signal Transduction of Eastern Hepatobiliary Surgery Institute | Ding J.,International Cooperation Laboratory on Signal Transduction of Eastern Hepatobiliary Surgery Institute | Sun W.,International Cooperation Laboratory on Signal Transduction of Eastern Hepatobiliary Surgery Institute | Fu J.,International Cooperation Laboratory on Signal Transduction of Eastern Hepatobiliary Surgery Institute | And 13 more authors.
Hepatology | Year: 2012

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. © 2012 American Association for the Study of Liver Diseases.

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