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Yes‐associated protein promotes cell migration via activating Wiskott‐Aldrich syndrome protein family member 1 in oral squamous cell carcinoma
Author(s) -
Qi Lei,
Shi Chaoji,
Li Jiayi,
Xu Shengming,
Han Yong,
Li Jiang,
Zhang Lei
Publication year - 2019
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/jop.12833
Subject(s) - cell migration , gene knockdown , cancer research , biology , cell , cell growth , oncogene , small interfering rna , blot , rna interference , motility , cell culture , microbiology and biotechnology , cell cycle , rna , transfection , gene , biochemistry , genetics
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 CA 3. 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 CA 3, 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, sh RNA interference, YAP re‐expression, and WAVE 1 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. CA 3 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 WAVE 1 overexpression in YAP ‐sh RNA stable cells. Conclusions The present study revealed that YAP was associated with cell migration and that this process was regulated by YAP / WAVE 1. We also demonstrated that CA 3 exhibited marked inhibitory effects on YAP expression and that it could be considered a potential therapeutic target for the treatment of OSCC .