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Dll4/Notch1 signalling pathway is required in collective invasion of salivary adenoid cystic carcinoma.

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机构: [1]State Key Laboratory of Oral Diseases, Department of Oral and Maxillofacial Surgery, National Clinical ResearchCenter for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041 [2]Department of General Dentistry, Hospital of Stomatology, Zunyi Medical University, Zunyi, Guizhou 563006 [3]Department of Head and Neck Surgery, Sichuan Cancer Institute, Sichuan Cancer Center, Sichuan Cancer Hospital,School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610000 [4]State Key Laboratory of Oral Diseases, Department of Oral Pathology, National Clinical Research Center for Oral Diseases,West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, P.R. China
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关键词: salivary adenoid cystic carcinoma δ‑like ligand 4 Notch1 collective invasion migration and invasion

摘要:
High expression of δ‑like ligand 4 (Dll4) is reportedly related to the invasion, metastasis, and clinical prognosis of various malignant tumours. Our previous study revealed that collective cell invasion was a common pattern in salivary adenoid cystic carcinoma (SACC). However, the roles of the Dll4/Notch1 signalling pathway in the collective invasion of SACC remain unclear. The present study revealed that Dll4 expression was higher at the invasive front of SACC, and that this upregulation was associated with solid tumour type, high TNM grade, and high rates of metastasis and recurrence. Furthermore, the expression levels of Notch1 and Dll4 were positively correlated at the invasive front, and a three‑dimensional (3D) culture model revealed that leader cells showed high expression of Dll4, while follower cells showed high expression of Notch1. Moreover, silencing of Dll4 expression using small interfering RNA reduced the migration, invasion, and collective invasion of SACC cells, and these abilities were rescued by Notch1 overexpression. Finally, SACC collective invasion was increased via the Dll4/Notch1 signalling pathway in experiments that involved a stiff 3D gel, hypoxia and co‑culture with human endothelial cells. These findings indicated that the Dll4/Notch1 signalling pathway may be involved in the collective invasion of SACC, which may help to provide possible targets for the treatment of SACC.

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基金编号: grant nos. 82073000, 81902779 and 81972542

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出版当年[2021]版:
大类 | 3 区 医学
小类 | 3 区 肿瘤学
最新[2023]版:
大类 | 3 区 医学
小类 | 4 区 肿瘤学
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Q3 ONCOLOGY
最新[2023]版:
Q2 ONCOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2021版] 出版当年五年平均 出版前一年[2020版] 出版后一年[2022版]

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第一作者机构: [1]State Key Laboratory of Oral Diseases, Department of Oral and Maxillofacial Surgery, National Clinical ResearchCenter for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041 [2]Department of General Dentistry, Hospital of Stomatology, Zunyi Medical University, Zunyi, Guizhou 563006
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通讯机构: [1]State Key Laboratory of Oral Diseases, Department of Oral and Maxillofacial Surgery, National Clinical ResearchCenter for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041 [4]State Key Laboratory of Oral Diseases, Department of Oral Pathology, National Clinical Research Center for Oral Diseases,West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, P.R. China [*1]State Key Laboratory of Oral Diseases, Department of Oral and Maxillofacial Surgery, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, 14 Renminnan Road, Chengdu, Sichuan 610041, P.R. China [*2]State Key Laboratory of Oral Diseases, Department of Oral Pathology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, 14 Renminnan Road, Chengdu, Sichuan 610041, P.R. China
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