FAM64A promotes HNSCC tumorigenesis by mediating transcriptional autoregulation of FOXM1.
10.1038/s41368-022-00174-4
- Author:
Xinyuan ZHAO
1
;
Huan CHEN
1
;
Yu QIU
2
;
Li CUI
3
Author Information
1. Stomatological Hospital, Southern Medical University, Guangzhou, China.
2. Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China. qy97@163.com.
3. Stomatological Hospital, Southern Medical University, Guangzhou, China. licui@smu.edu.cn.
- Publication Type:Journal Article
- MeSH:
Animals;
Carcinogenesis;
Cell Line, Tumor;
Cell Proliferation;
Cell Transformation, Neoplastic;
Head and Neck Neoplasms/genetics*;
Homeostasis;
Mice;
Squamous Cell Carcinoma of Head and Neck
- From:
International Journal of Oral Science
2022;14(1):25-25
- CountryChina
- Language:English
-
Abstract:
Head and neck squamous cell carcinoma (HNSCC) still lacks effective targeted treatment. Therefore, exploring novel and robust molecular targets is critical for improving the clinical outcome of HNSCC. Here, we reported that the expression levels of family with sequence similarity 64, member A (FAM64A) were significantly higher in HNSCC tissues and cell lines. In addition, FAM64A overexpression was found to be strongly associated with an unfavorable prognosis of HNSCC. Both in vitro and in vivo evidence showed that FAM64A depletion suppressed the malignant activities of HNSCC cells, and vice versa. Moreover, we found that the FAM64A level was progressively increased from normal to dysplastic to cancerous tissues in a carcinogenic 4-nitroquinoline-1-oxide mouse model. Mechanistically, a physical interaction was found between FAM64A and forkhead box protein M1 (FOXM1) in HNSCC cells. FAM64A promoted HNSCC tumorigenesis not only by enhancing the transcriptional activity of FOXM1, but also, more importantly, by modulating FOXM1 expression via the autoregulation loop. Furthermore, a positive correlation between FAM64A and FOXM1 was found in multiple independent cohorts. Taken together, our findings reveal a previously unknown mechanism behind the activation of FOXM1 in HNSCC, and FAM64A might be a promising molecular therapeutic target for treating HNSCC.
