Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Yang, Y; Liu, Y; He, JC; Wang, JM; Schemmer, P; Ma, CQ; Qian, YW; Yao, W; Zhang, J; Qi, WP; Fu, Y; Feng, W; Yang, T.
14-3-3ζ and aPKC-ι synergistically facilitate epithelial-mesenchymal transition of cholangiocarcinoma via GSK-3β/Snail signaling pathway.
Oncotarget. 2016; 7(34):55191-55210
Doi: 10.18632/oncotarget.10483
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- Leading authors Med Uni Graz
- Schemmer Peter
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- Abstract:
- Cholangiocarcinoma (CCA) invasion and metastasis are the primary causes of poor survival rates in patients. The epithelial-mesenchymal transition (EMT) is a crucial step in cancer invasion and metastasis. However, it is still unclear of the molecular mechanism. In this study, the expression of 14-3-3ζ and atypical protein kinase C-ι (aPKC-ι) was further detected in CCA tissues and cell lines. Meanwhile, we established the EMT model of CCA cells and investigated 14-3-3ζ and aPKC-ι co-regulatory effect on the EMT in vitro and in vivo. Further, we identified the downstream molecular glycogen synthase kinase 3 beta (GSK-3β)/Snail signalling pathway that contribute to regulating the EMT. Our data showed that the expression of 14-3-3ζ and aPKC-ι was synergistically increased in CCA tissues compared with adjacent noncancerous tissues and was intimately associated with differentiation and the tumour-node-metastasis (TNM) stage. Multivariate Cox regression analysis indicated that high 14-3-3ζ and aPKC-ι expression separately predicted a poor prognosis and were independent prognostic indicators in patients with CCA. The CO-IP experiment confirmed that the mutual binding relationship between 14-3-3ζ and aPKC-ι. Small interfering RNAs and siRNA rescue experiment demonstrated that 14-3-3ζ and aPKC-ι regulated each other. In addition, 14-3-3ζ and aPKC-ι pretreatment by si-RNA inhibit the phosphorylated GSK-3β and Snail expression during EMT. Meanwhile, silence of 14-3-3ζ or aPKC-ι suppressed CCA cells migration, metastasis and proliferation in vitro and in vivo. Our study demonstrates that 14-3-3ζ and aPKC-ι synergistically facilitate EMT of CCA via GSK-3β/Snail signalling pathway, and may be potential therapeutic target for CCA.
- Find related publications in this database (using NLM MeSH Indexing)
- 14-3-3 Proteins - physiology
- Animals -
- Bile Duct Neoplasms - etiology
- Bile Duct Neoplasms - mortality
- Bile Duct Neoplasms - pathology
- Cell Movement -
- Cell Proliferation -
- Cholangiocarcinoma - etiology
- Cholangiocarcinoma - mortality
- Cholangiocarcinoma - pathology
- Epithelial-Mesenchymal Transition -
- Female -
- Glycogen Synthase Kinase 3 beta - physiology
- Humans -
- Isoenzymes - physiology
- Mice -
- Mice, Inbred BALB C -
- Protein Kinase C - physiology
- Signal Transduction - physiology
- Snail Family Transcription Factors - physiology
- Find related publications in this database (Keywords)
- cholangiocarcinoma
- epithelial-mesenchymal transition
- synergy
- transfection
- silencing