Inhibition of DEC2 is necessary for exiting cell dormancy in salivary adenoid cystic carcinoma
Authors: Ya-Ling Tang
Mao Li
Mei Zhang
Xiang-Hua Yu
Xin Pang
Jia-Shun Wu
Xiao Yang
Wei-Long Zhang
Hao-Fan Wang
Xin-Hua Liang
Xiao-Lei Gao
Journal: Journal of Experimental & Clinical Cancer Research (2021)
Discipline: CLINICAL MEDICINE
Keywords: DEC2; EMT; Hypoxia microenvironment; Metastasis; Salivary adenoid cystic carcinoma
Affiliations: 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., State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology (Sichuan University), No.14, Sec. 3, Renminnan Road, Chengdu, 610041, China., 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. .

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. 

Retracted: No

PubPeer comments:
 Figure 1 C appears to have an overlap with Figure 5 B. This lab appears to have more than [a dozen papers](http: https: pubpeer.com search?q=authors%3A%22Ya-ling+Tang%22) with similar concerns.**   , 
 30 + 9 = 49uff1f P value = 8 ?  , 
 #2 Thank you very much for pointing out these for us. After checking Table 1carefully, we found that we made the mistake of writing 9 instead of 19 and we did not notice this. But the other data including P value are all correct. The P value was 0.0438, but during the typesetting process the last ending 8 was placed on the next ling, causing the P value to be 0.043 and 8 respectively. The original Table 1 was shown as follows.  #1 Thank you very much for pointing out this problem for us. After checking and verifying the original data carefully, we found this unconscious mistake because of some confusion during data consolidation process. The WB image of snail in Figure 5B was continuously placed in Figure 1C, so there was some overlap between these two figures. We provided the original WB image of actin in Figure 1C as follows. We are very sorry for this mistake and thanks again for your comment!  , 
 #1 and #3 Are there further mistakes between the following 2 WBs? That from P27 was vertically stretched and contrast enhanced to show details. Can the author please post the originals of the 2 involved WBs?  , 
 #4 Thank you very much for your comment. After checking the original data carefully, we confirmed that there was no mistake between the following 2 WBs that you proposed. As we can see there were obvious differences between the bands in the 2 WBs. And we also provided the original images of the 2 involved WBs as followings. Thanks again for your comment!  , 
 #5 Sir, I came across this old discussion today and thought I d contribute an image analysis. Taking the  original provided by you I edited the P27 band to better match the size, brightness and contrast of the DEC2 band and show the results below. To me, these seem unexpectedly highly similar. ***  ,