Soluble E-cadherin promotes invasiveness of neoplastic cells in salivary gland carcinoma ex pleomorphic adenoma.

Wanling Chen, Sai Ye, Xiaoning Wang, Jiajun Qian, Liang Xia, Zhen Tian

Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 2023 Jan

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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. 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. 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. 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. © 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Citation

Wanling Chen, Sai Ye, Xiaoning Wang, Jiajun Qian, Liang Xia, Zhen Tian. Soluble E-cadherin promotes invasiveness of neoplastic cells in salivary gland carcinoma ex pleomorphic adenoma. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 2023 Jan;52(1):63-71