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YAP is a critical oncogene in human cholangiocarcinoma
- Source :
- Oncotarget
- Publication Year :
- 2015
- Publisher :
- Impact Journals LLC, 2015.
-
Abstract
- Yes-associated protein (YAP), a transcriptional co-activator, has important regulatory roles in cell signaling and is dysregulated in a number of cancers. However, the role of YAP in cholangiocarcinoma (CCA) progression remains unclear. Here, we demonstrated that YAP was overexpressed in CCA cells and human specimens. High levels of nuclear YAP (nYAP) correlated with histological differentiation, TNM stage, metastasis and poor prognosis in CCA. Silencing YAP increased tumor sensitivity to chemotherapy and inhibited CCA tumorigenesis and metastasis both in vivo and in vitro. YAP overexpression in vivo and in vitro promoted CCA tumorigenesis and metastasis. Additionally, we found that YAP induced epithelial-mesenchymal transition (EMT) and formed a regulatory circuit with miR-29c, IGF1, AKT and gankyrin to promote the progression of CCA. Results of CCA tissue microarray showed positive correlations between nYAP and gankyrin or p-AKT expression. Combination of nYAP and gankyrin or p-AKT exhibited improved prognostic accuracy for CCA patients. In conclusion, YAP promotes carcinogenesis and metastasis by up-regulating gankyrin through activation of the AKT pathway.
- Subjects :
- Proteasome Endopeptidase Complex
Epithelial-Mesenchymal Transition
Gankyrin
gankyrin
Blotting, Western
information science
Fluorescent Antibody Technique
Enzyme-Linked Immunosorbent Assay
Kaplan-Meier Estimate
Biology
medicine.disease_cause
Metastasis
Cholangiocarcinoma
Cell Line, Tumor
Proto-Oncogene Proteins
parasitic diseases
medicine
Animals
Humans
Neoplasm Invasiveness
Epithelial–mesenchymal transition
cardiovascular diseases
Protein kinase B
PI3K/AKT/mTOR pathway
Adaptor Proteins, Signal Transducing
Mice, Inbred BALB C
Tissue microarray
Oncogene
AKT
fungi
YAP-Signaling Proteins
medicine.disease
Phosphoproteins
Up-Regulation
Gene Expression Regulation, Neoplastic
tumorigenesis
Cell Transformation, Neoplastic
Oncology
Bile Duct Neoplasms
Tissue Array Analysis
biology.protein
Cancer research
cardiovascular system
Heterografts
YAP
Carcinogenesis
Research Paper
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 19492553
- Volume :
- 6
- Issue :
- 19
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....13285dece203fee99178279d7592e18e