Involvement of 14-3-3 Proteins in Regulating Tumor Progression of Hepatocellular Carcinoma
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 assoc...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2015-06-01
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| Series: | Cancers |
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| Online Access: | http://www.mdpi.com/2072-6694/7/2/0822 |
| _version_ | 1797761762236301312 |
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| author | Yi-Ju Wu Yee-Jee Jan Bor-Sheng Ko Shu-Man Liang Jun-Yang Liou |
| author_facet | Yi-Ju Wu Yee-Jee Jan Bor-Sheng Ko Shu-Man Liang Jun-Yang Liou |
| author_sort | Yi-Ju Wu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T19:17:44Z |
| format | Article |
| id | doaj.art-2d871ce8efe34bbea7dbc1cab01b7a6c |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T19:17:44Z |
| publishDate | 2015-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-2d871ce8efe34bbea7dbc1cab01b7a6c2023-08-02T05:24:35ZengMDPI AGCancers2072-66942015-06-01721022103610.3390/cancers7020822cancers7020822Involvement of 14-3-3 Proteins in Regulating Tumor Progression of Hepatocellular CarcinomaYi-Ju Wu0Yee-Jee Jan1Bor-Sheng Ko2Shu-Man Liang3Jun-Yang Liou4Institute of Cellular and System Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan 350, TaiwanDepartment of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, Taichung 407, TaiwanDepartment of Internal Medicine, National Taiwan University Hospital, Taipei 100, TaiwanInstitute of Cellular and System Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan 350, TaiwanInstitute of Cellular and System Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan 350, TaiwanThere 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.http://www.mdpi.com/2072-6694/7/2/082214-3-3apoptosisepithelial-mesenchymal transitionhepatocellular carcinomamigrationproliferation |
| spellingShingle | Yi-Ju Wu Yee-Jee Jan Bor-Sheng Ko Shu-Man Liang Jun-Yang Liou Involvement of 14-3-3 Proteins in Regulating Tumor Progression of Hepatocellular Carcinoma Cancers 14-3-3 apoptosis epithelial-mesenchymal transition hepatocellular carcinoma migration proliferation |
| title | Involvement of 14-3-3 Proteins in Regulating Tumor Progression of Hepatocellular Carcinoma |
| title_full | Involvement of 14-3-3 Proteins in Regulating Tumor Progression of Hepatocellular Carcinoma |
| title_fullStr | Involvement of 14-3-3 Proteins in Regulating Tumor Progression of Hepatocellular Carcinoma |
| title_full_unstemmed | Involvement of 14-3-3 Proteins in Regulating Tumor Progression of Hepatocellular Carcinoma |
| title_short | Involvement of 14-3-3 Proteins in Regulating Tumor Progression of Hepatocellular Carcinoma |
| title_sort | involvement of 14 3 3 proteins in regulating tumor progression of hepatocellular carcinoma |
| topic | 14-3-3 apoptosis epithelial-mesenchymal transition hepatocellular carcinoma migration proliferation |
| url | http://www.mdpi.com/2072-6694/7/2/0822 |
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