Elevation of YAP promotes the epithelial-mesenchymal transition and tumor aggressiveness in colorectal cancer
Autor: | Cheng Wei Lin, Hsiang Hsi Ling, Yen Hua Huang, Chih Chia Kuo, Bo Xing Lin |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Epithelial-Mesenchymal Transition Indoles Colorectal cancer medicine.drug_class Biology Hydroxamic Acids medicine.disease_cause Metastasis 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Cell Movement Cell Line Tumor Panobinostat medicine Humans Epithelial–mesenchymal transition RNA Small Interfering Adaptor Proteins Signal Transducing Cell Proliferation Histone deacetylase inhibitor Cancer YAP-Signaling Proteins Cell Biology HCT116 Cells Phosphoproteins medicine.disease Up-Regulation 030104 developmental biology Cell culture 030220 oncology & carcinogenesis Cancer research Colorectal Neoplasms Carcinogenesis Transcription Factors |
Zdroj: | Experimental Cell Research. 350:218-225 |
ISSN: | 0014-4827 |
DOI: | 10.1016/j.yexcr.2016.11.024 |
Popis: | Tumor metastasis is the leading cause of death in cancer patients. Identifying metastatic biomarkers in tumor cells would help cancer diagnoses and the development of therapeutic targets. Yes-associated protein (YAP) plays an important role in organ development and has gained much attention in tumorigenesis. However, the role of YAP and the underlying mechanism in tumor metastasis of colorectal cancer (CRC) is still unclear. In this study, we generated metastatic 116-LM cells from the HCT116 CRC cell line. We found that the capacity for tumor aggressiveness was elevated in 116-LM cells and identified that YAP and its mRNA level were upregulated in 116-LM cells. Moreover, expression of YAP was found to correlate with epithelial-mesenchymal transition (EMT) marker expressions, whereas suppression of YAP decreased EMT marker expressions and impeded tumor migration and invasion. Additionally, upregulation of YAP was identified in colon cancer patients, and it was correlated with EMT gene expressions. Furthermore, we identified LBH589, a histone deacetylase inhibitor, that was capable of inhibiting tumor growth and aggressiveness in both HCT116 and 116-LM cells. LBH589 potentially inhibited YAP and its mRNA expression, accompanied by diminished expressions of YAP downstream genes and EMT markers. Together, YAP plays a crucial role in aggressiveness and metastasis of CRC, and YAP may be an attractive therapeutic target. |
Databáze: | OpenAIRE |
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