ASC contributes to metastasis of oral cavity squamous cell carcinoma
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Chi-Sheng Wu1,*, Kai-Ping Chang1,3,*, Chun-Nan OuYang1, Huang-Kai Kao4, Chuen Hsueh1,5, Lih-Chyang Chen6, Hsiao-Yun Cheng1, Ying Liang1, Willisa Liou7, Chih-lung Liang8, Yu-Sun Chang1,2,3
1Chang Gung Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan
2Graduate Institute of Basic Medical Sciences, Chang Gung University, Taoyuan, Taiwan
3Department of Otolaryngology-Head & Neck Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan
4Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan
5Department of Pathology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
6Department of Medicine, Mackay Medical College, New Taipei City, Taiwan
7Department of Anatomy, Chang Gung University, Taoyuan, Taiwan
8School of Medicine, Chung Shan Medical University, Taichung, Taiwan
*These authors have contributed equally to this work
Kai-Ping Chang, email: [email protected]
Yu-Sun Chang, email: [email protected]
Keywords: ASC, OSCC, metastasis
Received: September 09, 2015 Accepted: June 07, 2016 Published: June 29, 2016
ASC (Apoptosis-associated Speck-like protein containing a CARD) acts as a platform protein in the inflammasome cascade of some cancer types. However, its potential involvement in OSCC (oral cavity squamous cell carcinoma) has not yet been determined. Here, we investigated the potential role of ASC in OSCC. RT-qPCR analysis of 20 paired tumor and adjacent normal tissue samples revealed that the mRNA levels of ASC, along with IL-1β, CASP1, and NLRP3 in ASC-associated NLRP3 inflammasome were significantly elevated in OSCC tissues. Immunohistochemical staining of these four proteins in 111 clinical specimens revealed that high-level expression of ASC was significantly associated with tumor stage, node stage (p=0.001), overall stage (p<0.001), extracapsular spread (p<0.001), perineural invasion (p=0.004) and tumor depth (p<0.001). Kaplan-Meier survival analysis further revealed that high-level ASC expression was correlated with poorer overall survival (p=0.001), disease-specific survival (p<0.001) and disease-free survival (p<0.001). Studies using OSCC cell lines indicated that high-level ASC expression enhanced cell migration and invasion, and experiments using an orthotropic nude mouse model confirmed that ASC overexpression induced metastasis of OSCC cells. This is the first report to show that ASC contributes to OSCC metastasis, and that high-level ASC expression is a marker for poor prognosis in OSCC patients.
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