期刊
JOURNAL OF CANCER
卷 11, 期 2, 页码 364-373出版社
IVYSPRING INT PUBL
DOI: 10.7150/jca.32436
关键词
oral squamous cell carcinoma; AR-42; histone deacetylase; cancer stem cell
类别
资金
- National Natural Science Foundation of China [81300882, 81702286]
- Fundamental Research Funds of Science & Technology Department of Sichuan Province [2017YSKY0001]
- Chongqing Research Program of Basic Research and Frontier Technology [cstc2013jcyjA10042]
- Program for Innovation Team Building at Institutions of Higher Education in Chongqing in 2016
Oral squamous cell carcinoma (OSCC) is one of the most common malignancies worldwide. Although great progress has been made in diagnosis and treatment strategies in recent years, the 5-year survival rate of OSCC patients is still disappointingly low. Hence, there is still an unmet medical need for sufferers with OSCC. As a downstream effector of Hippo pathway, TAZ was up-regulated in multiple cancers including OSCC, and considered as an effective therapeutic target. In this study, we constructed a stable transfected cell line HEK293-TAZ to screen TAZ inhibitor using dual-luciferase reporter assay, and found a potential TAZ inhibitor AR-42. The results showed that AR-42 effectively suppressed the viability and proliferation of OSCC cells, and induced cellular apoptosis and cell cycle arrest in G2/M phase. Moreover, AR-42 potently inhibited cell invasion and the capacity of sphere-forming, as well as the expression of EMT and cancer stem cell related proteins in OSCC cells, exhibiting potential efficacy against OSCC metastasis and self-renewal of oral cancer stem cell. Further mechanism studies showed that AR-42 inhibited the total amount of TAZ and its paralog YAP mainly through blockade of TAZ/YAP transcription and promotion of TAZ/YAP protein degradation. Additionally, the inhibitory effect of AR-42 against TAZ, as well as its anti-OSCC activity could be also observed in SCC9 xenograft model. Taken together, AR-42 deserves to be further studied as a TAZ inhibitor, and is worthy to be further assessed as a potential drug candidate for OSCC treatment.
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