TY - JOUR
T1 - Elevation of YAP promotes the epithelial-mesenchymal transition and tumor aggressiveness in colorectal cancer
AU - Ling, Hsiang Hsi
AU - Kuo, Chih Chia
AU - Lin, Bo Xing
AU - Huang, Yen Hua
AU - Lin, Cheng Wei
N1 - Funding Information:
This study was supported grants from the Ministry of Science and Technology, Taiwan (MOST104-2320-B-038–048 to C.W. Lin) and Taipei Medical University (TMUTOP103005-7 to C.W. Lin and TMU-T104-06 to Y.H. Huang), Taiwan.
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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.
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.
KW - Colon cancer
KW - Epithelia-mesenchymal transition (EMT)
KW - LBH589
KW - Metastasis
KW - Yes-associated protein (YAP)
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UR - http://www.scopus.com/inward/citedby.url?scp=85006974085&partnerID=8YFLogxK
U2 - 10.1016/j.yexcr.2016.11.024
DO - 10.1016/j.yexcr.2016.11.024
M3 - Article
C2 - 27914787
AN - SCOPUS:85006974085
SN - 0014-4827
VL - 350
SP - 218
EP - 225
JO - Experimental Cell Research
JF - Experimental Cell Research
IS - 1
ER -
