Cancers | |
Involvement of 14-3-3 Proteins in Regulating Tumor Progression of Hepatocellular Carcinoma | |
Yi-Ju Wu3  Yee-Jee Jan2  Bor-Sheng Ko1  Shu-Man Liang3  Jun-Yang Liou3  | |
[1] Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan; E-Mail:;Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, Taichung 407, Taiwan; E-Mail:;Institute of Cellular and System Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan 350, Taiwan; E-Mails: | |
关键词: 14-3-3; apoptosis; epithelial-mesenchymal transition; hepatocellular carcinoma; migration; proliferation; | |
DOI : 10.3390/cancers7020822 | |
来源: mdpi | |
【 摘 要 】
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.
【 授权许可】
CC BY
© 2015 by the authors; licensee MDPI, Basel, Switzerland.
【 预 览 】
Files | Size | Format | View |
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RO202003190010780ZK.pdf | 276KB | download |