Inhibition of DEC2 is necessary for exiting cell dormancy in salivary adenoid cystic carcinoma.
Inhibition of DEC2 is necessary for exiting cell dormancy in salivary adenoid cystic carcinoma.
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DOI：
10.1186/s13046-021-01956-0
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发表时间：
2021-05-14
期刊：
影响因子：
--
通讯作者：
Tang YL
中科院分区：
文献类型：
--
作者：
Yang X;Wu JS;Li M;Zhang WL;Gao XL;Wang HF;Yu XH;Pang X;Zhang M;Liang XH;Tang YL
一旦休眠的肿瘤细胞被重新激活，患者的预后往往很差。然而，肿瘤细胞休眠的分子机制仍然知之甚少。本研究旨在探讨DEC 2在体内外涎腺腺样囊性癌（SACC）细胞休眠中的作用。通过建立裸鼠SACC原发和肺转移模型，研究DEC 2在SACC肿瘤休眠中的作用。同时，通过CoCl 2诱导的模拟缺氧微环境，揭示了缺氧与SACC休眠的相互作用以及DEC 2的作用。免疫组化法检测DEC 2在原发性SACC和无复发SACC中的表达。在原代SACC中，DEC 2过表达抑制细胞增殖，增加停滞在G 0/G1期的细胞数量，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，DEC 2的水平显著降低，导致SACC细胞休眠退出和生长恢复。因此，我们发现DEC 2可能与缺氧有关，从而促进肿瘤休眠，这可能为解释DEC 2在原发性和转移性病变中的不同作用提供了可能的线索。DEC 2的过表达可诱导植物休眠，并通过激活EMT程序促进植物的迁移和入侵。最后，DEC 2阳性表达与SACC患者的复发和休眠显着相关。这些发现为深入研究DEC 2基因在肿瘤休眠和转移中的作用提供了新的思路。在线版本包含补充材料，可通过10.1186/s13046-021-01956-0获得。
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 CoCl2 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. The online version contains supplementary material available at 10.1186/s13046-021-01956-0.
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