CCL18 Induces EMT via CEP192 Down-Regulation in Breast Cancer

Background: Chemokine (C-C motif) ligand 18 (CCL18) secreted by TAMs induces epithelial-mesenchymal transformation (EMT) in breast cancer cells. Centrosome scaffold protein KDA192 (CEP192) ,as the important pericentriolar material (PCM), plays a critical role in microtubule nucleation and centrosome replication. Decreased expression of CEP192 will cause tumor cell polarization and elevated motility. Whether CEP192 is involved in the process of breast cancer EMT induced by CCL18 has not been reported. Methods: : CEP192 mRNA level in Lymph node metastasis and non-lymph node metastasis breast cancer was evaluated by bioinformatics analysis. CCL18 and CEP192 expressions in breast tissues were examined using immunochemistry, CEP192 expression in breast cancer cells was examined using qPCR and Western blot. CEP192 was silenced using siRNA. EMT phenotype proteins were examined using Western blot. Statistical analysis was performed using GraphPad Prism 8.0 (GraphPad Software Inc). Results: : CEP192 expression was decreased in lymph node metastasis breast cancer tissues compared with non-lymph node metastasis. CEP192 expression was down-regulated by CCL18 in breast cancer cells and silencing CEP192 promoted the migration and invasion of cancer cells. Based on the promotion of breast cancer EMT by CCL18, silencing CEP192 in breast cancer further increased E-cadherin and decreased KRT-8which are both EMT phenotype proteins in vitro. Conclusions: : Our study elucidates that CCL18 promotes breast cancer EMT by down-regulating CEP192 expression. Down-regulated CEP192 plays a key role in invasion and migration of breast cancer cells. CEP192 is a potential new marker for tumor metastasis induced by CCL18.