Open Access

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

  • Authors:
    • Ke Wang
    • Hua‑Yang Fan
    • Xing Pang
    • Mei Zhang
    • Xiang‑Hua Yu
    • Jia‑Shun Wu
    • Bing‑Jun Chen
    • Jian Jiang
    • Xin‑Hua Liang
    • Ya‑Ling Tang
  • View Affiliations

  • Published online on: January 18, 2021     https://doi.org/10.3892/or.2021.7939
  • Pages: 1011-1022
  • Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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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March-2021
Volume 45 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Copy and paste a formatted citation
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Spandidos Publications style
Wang K, Fan HY, Pang X, Zhang M, Yu XH, Wu JS, Chen BJ, Jiang J, Liang XH, Tang YL, Tang YL, et al: Dll4/Notch1 signalling pathway is required in collective invasion of salivary adenoid cystic carcinoma. Oncol Rep 45: 1011-1022, 2021
APA
Wang, K., Fan, H., Pang, X., Zhang, M., Yu, X., Wu, J. ... Tang, Y. (2021). Dll4/Notch1 signalling pathway is required in collective invasion of salivary adenoid cystic carcinoma. Oncology Reports, 45, 1011-1022. https://doi.org/10.3892/or.2021.7939
MLA
Wang, K., Fan, H., Pang, X., Zhang, M., Yu, X., Wu, J., Chen, B., Jiang, J., Liang, X., Tang, Y."Dll4/Notch1 signalling pathway is required in collective invasion of salivary adenoid cystic carcinoma". Oncology Reports 45.3 (2021): 1011-1022.
Chicago
Wang, K., Fan, H., Pang, X., Zhang, M., Yu, X., Wu, J., Chen, B., Jiang, J., Liang, X., Tang, Y."Dll4/Notch1 signalling pathway is required in collective invasion of salivary adenoid cystic carcinoma". Oncology Reports 45, no. 3 (2021): 1011-1022. https://doi.org/10.3892/or.2021.7939