Abstract
BackgroundPatients 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.MethodsThe function of DEC2 in tumor dormancy of SACC was investigated in nude mice by establishing primary and lung metastasis model. Meanwhile, the interaction between hypoxia and SACC dormancy and the role of DEC2 were demonstrated through CoCl2 induced hypoxia–mimicking microenvironments. Furthermore, the expression of DEC2 was detected by immunohistochemical staining in primary SACC samples with and without recurrence.ResultsIn 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.ConclusionsThese findings provide a novel insight into the role of DEC2 gene in tumor dormancy and metastasis.
Highlights
Patients were prone to have poor prognosis once dormant tumor cells being reactivated
DEC2 may associate with HIF1α in contributing to tumor dormancy, which might provide a possible cue to explain the different roles of DEC2 in primary and metastasis lesions
The data showed that upregulation of DEC2 involved in atRA treatment contributing to tumor dormancy of the xenograft model
Summary
Patients were prone to have poor prognosis once dormant tumor cells being reactivated. Salivary adenoid cystic carcinoma (SACC) is one of the most common malignancies characterized with slow growth, but high incidence of local recurrence and metastasis [1, 2]. Tumor dormancy was a period in tumor progression in which residual disease existed but remained asymptomatic clinically for years or even decades [4]. It may appear during the formation of primary tumor, after dissemination of primary tumor cells or in the micrometastasis [5, 6]. Dormant tumor cells are emerging as a critical cause for recurrence and metastasis once they escape this state [8]. How tumor cells enter into dormancy and what processes govern their exit in human cancers including SACC are still absent and remain unclear
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