Involvement of 14-3-3 Proteins in Regulating Tumor Progression of Hepatocellular Carcinoma
AbstractThere 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
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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.
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(2):1022-1036.Chicago/Turabian Style
Wu, Yi-Ju; Jan, Yee-Jee; Ko, Bor-Sheng; Liang, Shu-Man; Liou, Jun-Yang. 2015. "Involvement of 14-3-3 Proteins in Regulating Tumor Progression of Hepatocellular Carcinoma." Cancers 7, no. 2: 1022-1036.