Downregulation of ceramide synthase 1 promotes oral cancer through endoplasmic reticulum stress.
10.1038/s41368-021-00118-4
- Author:
Wen CHEN
1
;
Chenzhou WU
1
;
Yafei CHEN
1
;
Yuhao GUO
1
;
Ling QIU
1
;
Zhe LIU
1
;
Haibin SUN
2
;
Siyu CHEN
1
;
Zijian AN
1
;
Zhuoyuan ZHANG
1
;
Yi LI
3
;
Longjiang LI
4
Author Information
1. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
2. Department of Oral and Maxillofacial-Head and Neck Oncology, Capital Medical University School of Stomatology, Beijing, China.
3. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, China. liyi1012@163.com.
4. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, China. muzili63@163.com.
- Publication Type:Research Support, Non-U.S. Gov't
- MeSH:
Animals;
Apoptosis;
Carcinoma, Squamous Cell;
Cell Line, Tumor;
Down-Regulation;
Endoplasmic Reticulum Stress;
Head and Neck Neoplasms;
Mice;
Mouth Neoplasms;
Oxidoreductases
- From:
International Journal of Oral Science
2021;13(1):10-10
- CountryChina
- Language:English
-
Abstract:
C18 ceramide plays an important role in the occurrence and development of oral squamous cell carcinoma. However, the function of ceramide synthase 1, a key enzyme in C18 ceramide synthesis, in oral squamous cell carcinoma is still unclear. The aim of our study was to investigate the relationship between ceramide synthase 1 and oral cancer. In this study, we found that the expression of ceramide synthase 1 was downregulated in oral cancer tissues and cell lines. In a mouse oral squamous cell carcinoma model induced by 4-nitroquinolin-1-oxide, ceramide synthase 1 knockout was associated with the severity of oral malignant transformation. Immunohistochemical studies showed significant upregulation of PCNA, MMP2, MMP9, and BCL2 expression and downregulation of BAX expression in the pathological hyperplastic area. In addition, ceramide synthase 1 knockdown promoted cell proliferation, migration, and invasion in vitro. Overexpression of CERS1 obtained the opposite effect. Ceramide synthase 1 knockdown caused endoplasmic reticulum stress and induced the VEGFA upregulation. Activating transcription factor 4 is responsible for ceramide synthase 1 knockdown caused VEGFA transcriptional upregulation. In addition, mild endoplasmic reticulum stress caused by ceramide synthase 1 knockdown could induce cisplatin resistance. Taken together, our study suggests that ceramide synthase 1 is downregulated in oral cancer and promotes the aggressiveness of oral squamous cell carcinoma and chemotherapeutic drug resistance.
