Epithelial-mesenchymal transition and anoikis resistance induced by Ang2 in salivary adenoid cystic carcinoma

Abstract

Patients, who suffer from Salivary Adenoid Cystic Carcinoma (SACC), face a heightened risk of recurrent or metastatic disease attributed to significant neuroinvasion, even with standard treatment, highlighting the imperative for innovative treatment targets and approaches. Our research indicates that the expression of angiopoietin-2 (Ang2) in the cytoplasm and nucleus of SACC tissue is significantly higher than that of normal tissue adjacent to cancer, which is related to the pathological type of the tissue. Approximately 74.2% of SACC express Ang2, which promotes survival and lung metastasis. In SACC cells, downregulation of Ang2 inhibits cell migration and enhances cell apoptosis, and resistance to cell apoptosis is deemed essential for metastasis. The downregulation of Ang2 leads to the restoration of E-cadherin levels by facilitating the proteasome-dependent degradation of its suppressor Snail.Overexpression of Snail prevented the complete inhibitory effect of Ang2 on ACC cell migration, which was in line with the promotion of epithelial mesenchymal transition (EMT). The in vivo findings demonstrated reduced lung colonization in conjunction with the downregulation of Ang2. Our findings illustrate Ang2 triggers EMT and enhances metastasis in SACC, suggesting that Ang2 could act to be a promising therapeutic option towards individuals with SACC.