Journal of Experimental & Clinical Cancer Research (May 2021)

Inhibition of DEC2 is necessary for exiting cell dormancy in salivary adenoid cystic carcinoma

  • Xiao Yang,
  • Jia-shun Wu,
  • Mao Li,
  • Wei-long Zhang,
  • Xiao-lei Gao,
  • Hao-fan Wang,
  • Xiang-hua Yu,
  • Xin Pang,
  • Mei Zhang,
  • Xin-hua Liang,
  • Ya-ling Tang

DOI
https://doi.org/10.1186/s13046-021-01956-0
Journal volume & issue
Vol. 40, no. 1
pp. 1 – 13

Abstract

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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 The 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. 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.

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