Inhibition of DEC2 is necessary for exiting cell dormancy in salivary adenoid cystic carcinoma
Xiao Yang, Jia‐shun Wu, Mao Li, Wei-long Zhang, Xiaolei Gao, Haofan Wang, Xianghua Yu, Xin Pang, Mei Zhang, Xinhua Liang, Ya‐ling Tang
Abstract
BACKGROUND: Patients were prone to have poor prognosis once dormant tumor cells being reactivated. However, the molecular mechanism of tumor cell dormancy remains poorly understood. This study aimed to investigate the function of DEC2 in the dormancy of salivary adenoid cystic carcinoma (SACC) in vitro and vivo. METHODS: induced hypoxia-mimicking microenvironments. Furthermore, the expression of DEC2 was detected by immunohistochemical staining in primary SACC samples with and without recurrence. RESULTS: In the primary SACC, DEC2 overexpression inhibited cell proliferation, increased cell population arrested in G0/G1 phase, and participated in dormancy regulation, which limited tumor growth. Intriguingly, in the model of lung metastasis, the level of DEC2 was reduced significantly and resulted in dormancy exit and growth resumption of SACC cells. Then, we found that DEC2 may associate with hypoxia in contributing to tumor dormancy, which might provide a possible cue to explain the different roles of DEC2 in primary and metastasis lesions. And overexpression of DEC2 induced dormancy and promoted migration and invasion through activating EMT program. Finally, DEC2 positive expression was shown to be significantly correlated with recurrence and dormancy of SACC patients. CONCLUSIONS: These findings provide a novel insight into the role of DEC2 gene in tumor dormancy and metastasis.