State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral Pathology, West China Hospital of Stomatology (Sichuan University), No.14, Sec. 3, Renminnan Road, Chengdu, 610041, China.
Department of Stomatology, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, China.
J Exp Clin Cancer Res. 2021 May 14;40(1):169. doi: 10.1186/s13046-021-01956-0.
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.
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 CoCl induced hypoxia-mimicking microenvironments. Furthermore, the expression of DEC2 was detected by immunohistochemical staining in primary SACC samples with and without recurrence.
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.
These findings provide a novel insight into the role of DEC2 gene in tumor dormancy and metastasis.
一旦休眠肿瘤细胞被重新激活，患者往往预后不良。然而，肿瘤细胞休眠的分子机制仍知之甚少。本研究旨在探讨 DEC2 在唾液腺腺样囊性癌（SACC）体外和体内休眠中的作用。
通过建立原发和肺转移模型，在裸鼠中研究 DEC2 在 SACC 休眠中的功能。同时，通过 CoCl 诱导的模拟缺氧微环境，证明了缺氧与 SACC 休眠的相互作用以及 DEC2 的作用。此外，通过免疫组化染色检测原发 SACC 样本中有无复发时 DEC2 的表达。
在原发 SACC 中，过表达 DEC2 抑制细胞增殖，增加 G0/G1 期细胞群体停滞，并参与休眠调节，从而限制肿瘤生长。有趣的是，在肺转移模型中，DEC2 的水平显著降低，导致 SACC 细胞休眠退出和生长恢复。然后，我们发现 DEC2 可能与缺氧有关，共同参与肿瘤休眠，这可能为解释 DEC2 在原发和转移病变中的不同作用提供了一个可能的线索。此外，过表达 DEC2 通过激活 EMT 程序诱导休眠，并促进迁移和侵袭。最后，DEC2 的阳性表达与 SACC 患者的复发和休眠显著相关。
这些发现为 DEC2 基因在肿瘤休眠和转移中的作用提供了新的见解。
