Elevation of YAP promotes the epithelial-mesenchymal transition and tumor aggressiveness in colorectal cancer

Hsiang Hsi Ling, Chih Chia Kuo, Bo Xing Lin, Yen Hua Huang, Cheng Wei Lin

研究成果: 雜誌貢獻文章

28 引文 (Scopus)

摘要

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.

原文英語
頁(從 - 到)218-225
頁數8
期刊Experimental Cell Research
350
發行號1
DOIs
出版狀態已發佈 - 一月 1 2017

指紋

Epithelial-Mesenchymal Transition
Colorectal Neoplasms
Neoplasms
Proteins
Neoplasm Metastasis
HCT116 Cells
Messenger RNA
Histone Deacetylase Inhibitors
Tumor Biomarkers
Colonic Neoplasms
Cause of Death
Carcinogenesis
Up-Regulation
Gene Expression
Cell Line

ASJC Scopus subject areas

  • Cell Biology

引用此文

Elevation of YAP promotes the epithelial-mesenchymal transition and tumor aggressiveness in colorectal cancer. / Ling, Hsiang Hsi; Kuo, Chih Chia; Lin, Bo Xing; Huang, Yen Hua; Lin, Cheng Wei.

於: Experimental Cell Research, 卷 350, 編號 1, 01.01.2017, p. 218-225.

研究成果: 雜誌貢獻文章

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AB - 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.

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