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Cancers 2015, 7(2), 1022-1036;

Involvement of 14-3-3 Proteins in Regulating Tumor Progression of Hepatocellular Carcinoma

Institute of Cellular and System Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan 350, Taiwan
Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, Taichung 407, Taiwan
Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan
These authors contributed equally to this work.
Author to whom correspondence should be addressed.
Academic Editor: Vita Golubovskaya
Received: 4 May 2015 / Accepted: 10 June 2015 / Published: 15 June 2015
(This article belongs to the Special Issue Cancer Cell Proliferation)
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There are seven mammalian isoforms of the 14-3-3 protein, which regulate multiple cellular functions via interactions with phosphorylated partners. Increased expression of 14-3-3 proteins contributes to tumor progression of various malignancies. Several isoforms of 14-3-3 are overexpressed and associate with higher metastatic risks and poorer survival rates of hepatocellular carcinoma (HCC). 14-3-3β and 14-3-3ζ regulate HCC cell proliferation, tumor growth and chemosensitivity via modulating mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK) and p38 signal pathways. Moreover, 14-3-3ε suppresses E-cadherin and induces focal adhesion kinase (FAK) expression, thereby enhancing epithelial-mesenchymal transition (EMT) and HCC cell migration. 14-3-3ζ forms complexes with αB-crystallin, which induces EMT and is the cause of sorafenib resistance in HCC. Finally, a recent study has indicated that 14-3-3σ induces heat shock protein 70 (HSP70) expression, which increases HCC cell migration. These results suggest that selective 14-3-3 isoforms contribute to cell proliferation, EMT and cell migration of HCC by regulating distinct targets and signal pathways. Targeting 14-3-3 proteins together with specific downstream effectors therefore has potential to be therapeutic and prognostic factors of HCC. In this article, we will overview 14-3-3's regulation of its downstream factors and contributions to HCC EMT, cell migration and proliferation. View Full-Text
Keywords: 14-3-3; apoptosis; epithelial-mesenchymal transition; hepatocellular carcinoma; migration; proliferation 14-3-3; apoptosis; epithelial-mesenchymal transition; hepatocellular carcinoma; migration; proliferation

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Wu, Y.-J.; Jan, Y.-J.; Ko, B.-S.; Liang, S.-M.; Liou, J.-Y. Involvement of 14-3-3 Proteins in Regulating Tumor Progression of Hepatocellular Carcinoma. Cancers 2015, 7, 1022-1036.

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