ASC contributes to metastasis of oral cavity squamous cell carcinoma

被引:30
作者
Wu, Chi-Sheng [1 ]
Chang, Kai-Ping [1 ,3 ,4 ]
OuYang, Chun-Nan [1 ]
Kao, Huang-Kai [5 ]
Hsueh, Chuen [1 ,6 ]
Chen, Lih-Chyang [7 ]
Cheng, Hsiao-Yun [1 ]
Liang, Ying [1 ]
Liou, Willisa [8 ]
Liang, Chih-Lung [9 ]
Chang, Yu-Sun [1 ,2 ,3 ,4 ]
机构
[1] Chang Gung Univ, Chang Gung Mol Med Res Ctr, Taoyuan, Taiwan
[2] Chang Gung Univ, Grad Inst Basic Med Sci, Taoyuan, Taiwan
[3] Chang Gung Mem Hosp, Dept Otolaryngol, Taoyuan, Taiwan
[4] Chang Gung Mem Hosp, Dept Head & Neck Surg, Taoyuan, Taiwan
[5] Chang Gung Mem Hosp, Dept Plast & Reconstruct Surg, Taoyuan, Taiwan
[6] Chang Gung Mem Hosp, Dept Pathol, Taoyuan, Taiwan
[7] Mackay Med Coll, Dept Med, New Taipei City, Taiwan
[8] Chang Gung Univ, Dept Anat, Taoyuan, Taiwan
[9] Chung Shan Med Univ, Sch Med, Taichung, Taiwan
关键词
ASC; OSCC; metastasis; CASPASE RECRUITMENT DOMAIN; SPECK-LIKE PROTEIN; NLRP3; INFLAMMASOME; ACTIVATING ADAPTER; CANCER; METHYLATION; GENE; APOPTOSIS; EXPRESSION; INTERLEUKIN-1-BETA;
D O I
10.18632/oncotarget.10317
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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-1 beta, 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 highlevel ASC expression was correlated with poorer overall survival (p= 0.001), diseasespecific 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.
引用
收藏
页码:50074 / 50085
页数:12
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