Lei Qi1,2,3, Chaoji Shi2,3,4, Jiayi Li2,3,4, Shengming Xu2,3,4, Yong Han2,3,4, Jiang Li2,3,5, Lei Zhang1,2,3. 1. Department of Oral and Cranio-maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 2. National Clinical Research Center for Oral Diseases, Shanghai Ninth People's Hospital, Shanghai, China. 3. Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, Shanghai, China. 4. Department of Oral and Maxillofacial-Head Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 5. Departmentof Oral Pathology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Abstract
BACKGROUND: Yes-associated protein (YAP) is a candidate oncogene in various cancers including oral squamous cell carcinoma (OSCC). Our previous study demonstrated that TNF-alpha could inhibit cell proliferation and invasion by YAP phosphorylation in OSCC. However, the role of YAP in OSCC is not yet clear. The objective of the present study was to elucidate the function of YAP in promoting migration in OSCC and to explore the possible mechanism with a novel YAP inhibitor CA3. METHODS: A total of 68 OSCC patients were enrolled, and the expression levels of YAP were investigated in tissue specimens by immunohistochemical staining. The inhibitory effects of CA3, a novel inhibitor of YAP, were demonstrated by immunofluorescence, Western blotting, and transwell assays. A human PCR motility array was performed to screen the changes in the gene expression profiles of the cells. In addition, shRNA interference, YAP re-expression, and WAVE1 overexpression plasmids were used to detect the regulatory mechanism of YAP and its relationship with cell migration. RESULTS: Yes-associated protein nuclear expression levels were associated with metastasis and 5-year overall survival rate. CA3 exhibited potent inhibitory effects on OSCC migration. YAP knockdown significantly suppressed tumor cell migration in OSCC. These effects were rescued when YAP was re-expressed and during WAVE1 overexpression in YAP-shRNA stable cells. CONCLUSIONS: The present study revealed that YAP was associated with cell migration and that this process was regulated by YAP/WAVE1. We also demonstrated that CA3 exhibited marked inhibitory effects on YAP expression and that it could be considered a potential therapeutic target for the treatment of OSCC.
BACKGROUND:Yes-associated protein (YAP) is a candidate oncogene in various cancers including oral squamous cell carcinoma (OSCC). Our previous study demonstrated that TNF-alpha could inhibit cell proliferation and invasion by YAP phosphorylation in OSCC. However, the role of YAP in OSCC is not yet clear. The objective of the present study was to elucidate the function of YAP in promoting migration in OSCC and to explore the possible mechanism with a novel YAP inhibitor CA3. METHODS: A total of 68 OSCC patients were enrolled, and the expression levels of YAP were investigated in tissue specimens by immunohistochemical staining. The inhibitory effects of CA3, a novel inhibitor of YAP, were demonstrated by immunofluorescence, Western blotting, and transwell assays. A human PCR motility array was performed to screen the changes in the gene expression profiles of the cells. In addition, shRNA interference, YAP re-expression, and WAVE1 overexpression plasmids were used to detect the regulatory mechanism of YAP and its relationship with cell migration. RESULTS:Yes-associated protein nuclear expression levels were associated with metastasis and 5-year overall survival rate. CA3 exhibited potent inhibitory effects on OSCC migration. YAP knockdown significantly suppressed tumor cell migration in OSCC. These effects were rescued when YAP was re-expressed and during WAVE1 overexpression in YAP-shRNA stable cells. CONCLUSIONS: The present study revealed that YAP was associated with cell migration and that this process was regulated by YAP/WAVE1. We also demonstrated that CA3 exhibited marked inhibitory effects on YAP expression and that it could be considered a potential therapeutic target for the treatment of OSCC.
Authors: Yiran Peng; Shoushan Hu; Kun Zhang; Yuru Wang; Maierdanjiang Rouzi; Dan Zhou; Ran Yang Journal: Cancer Manag Res Date: 2021-06-17 Impact factor: 3.989