Abstract

Background Soluble E-cadherin (sEcad), a tumor suppressor gene, has pro-oncogenic effects by binding to human epithelial growth factor receptor 2 ( HER-2 ). In our previous study, 1/3 of carcinoma ex pleomorphic adenoma (CXPA) cases had HER-2 amplification, which is associated with tumorigenesis and malignancy. This study examines the role of sEcad in HER-2 amplified CXPA. Methods Immunohistochemistry was used to examine E-cadherin (Ecad) expression in HER-2 -amplified CXPA samples ( n = 35). Western blot and ELISA were used to detect sEcad in two samples with Ecad and HER-2 overexpression and CXPA cell line. Lentivirus-mediated transfection was performed to knock down sEcad in CXPA cells. The cell proliferation, wound healing, and transwell assays were used to compare sEcad-knockdown cells with cells pretreated with recombinant human sEcad (rhEcad/Fc). sEcad and HER-2 interaction was determined through co-immunoprecipitation. RNA-sequencing, differential expression analysis, GO and KEGG analysis were used to identify sEcad - related signaling pathways and their protein phosphorylation levels were verified by western blotting. Results Ecad was overexpressed in 77.1% of HER-2 -positive CXPA, and sEcad was found in the CXPA cell line and two samples. sEcad promoted CXPA migration and invasion in vitro without sEcad and HER-2 interaction. sEcad-related differentially expressed genes were enriched in the IL-17, cAMP, and MAPK signaling pathways. Furthermore, sEcad activated the phosphorylation of Akt and MAPK/ERK signaling pathways. Conclusions Most HER-2 + CXPAs express Ecad. sEcad could affect the invasiveness and migration of in vitro CXPA cells without HER-2. sEcad may be a therapeutic biomarker for CXPA patients.