title: Involvement of 14-3-3 Proteins in Regulating Tumor Progression of Hepatocellular Carcinoma.
abstract: 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.
authors.affiliation: Institute of Cellular and System Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan 350, Taiwan. kathy614@nhri.org.tw.
authors.forename: Yi-Ju
authors.initials: YJ
authors.lastname: Wu
authors.affiliation: Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, Taichung 407, Taiwan. yejan@vghtc.gov.tw.
authors.forename: Yee-Jee
authors.initials: YJ
authors.lastname: Jan
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan. kevinkomd@gmail.com.
authors.forename: Bor-Sheng
authors.initials: BS
authors.lastname: Ko
authors.affiliation: Institute of Cellular and System Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan 350, Taiwan. shu-man@nhri.org.tw.
authors.forename: Shu-Man
authors.initials: SM
authors.lastname: Liang
authors.affiliation: Institute of Cellular and System Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan 350, Taiwan. jliou@nhri.org.tw.
authors.forename: Jun-Yang
authors.initials: JY
authors.lastname: Liou
keywords: 14-3-3; apoptosis; epithelial-mesenchymal transition; hepatocellular carcinoma; migration; proliferation