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

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 vi...

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Autores principales: Yang, Xiao, Wu, Jia-shun, Li, Mao, Zhang, Wei-long, Gao, Xiao-lei, Wang, Hao-fan, Yu, Xiang-hua, Pang, Xin, Zhang, Mei, Liang, Xin-hua, Tang, Ya-ling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120837/
https://www.ncbi.nlm.nih.gov/pubmed/33990215
http://dx.doi.org/10.1186/s13046-021-01956-0
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author Yang, Xiao
Wu, Jia-shun
Li, Mao
Zhang, Wei-long
Gao, Xiao-lei
Wang, Hao-fan
Yu, Xiang-hua
Pang, Xin
Zhang, Mei
Liang, Xin-hua
Tang, Ya-ling
author_facet Yang, Xiao
Wu, Jia-shun
Li, Mao
Zhang, Wei-long
Gao, Xiao-lei
Wang, Hao-fan
Yu, Xiang-hua
Pang, Xin
Zhang, Mei
Liang, Xin-hua
Tang, Ya-ling
author_sort Yang, Xiao
collection PubMed
description 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 CoCl(2) 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13046-021-01956-0.
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spelling pubmed-81208372021-05-17 Inhibition of DEC2 is necessary for exiting cell dormancy in salivary adenoid cystic carcinoma Yang, Xiao Wu, Jia-shun Li, Mao Zhang, Wei-long Gao, Xiao-lei Wang, Hao-fan Yu, Xiang-hua Pang, Xin Zhang, Mei Liang, Xin-hua Tang, Ya-ling J Exp Clin Cancer Res Research 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 CoCl(2) 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13046-021-01956-0. BioMed Central 2021-05-14 /pmc/articles/PMC8120837/ /pubmed/33990215 http://dx.doi.org/10.1186/s13046-021-01956-0 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Yang, Xiao
Wu, Jia-shun
Li, Mao
Zhang, Wei-long
Gao, Xiao-lei
Wang, Hao-fan
Yu, Xiang-hua
Pang, Xin
Zhang, Mei
Liang, Xin-hua
Tang, Ya-ling
Inhibition of DEC2 is necessary for exiting cell dormancy in salivary adenoid cystic carcinoma
title Inhibition of DEC2 is necessary for exiting cell dormancy in salivary adenoid cystic carcinoma
title_full Inhibition of DEC2 is necessary for exiting cell dormancy in salivary adenoid cystic carcinoma
title_fullStr Inhibition of DEC2 is necessary for exiting cell dormancy in salivary adenoid cystic carcinoma
title_full_unstemmed Inhibition of DEC2 is necessary for exiting cell dormancy in salivary adenoid cystic carcinoma
title_short Inhibition of DEC2 is necessary for exiting cell dormancy in salivary adenoid cystic carcinoma
title_sort inhibition of dec2 is necessary for exiting cell dormancy in salivary adenoid cystic carcinoma
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120837/
https://www.ncbi.nlm.nih.gov/pubmed/33990215
http://dx.doi.org/10.1186/s13046-021-01956-0
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