Global analysis of lysine acetylome reveals the potential role of CCL18 in non-small cell lung cancer.

ABSTRACT

C-C motif chemokine 18 (CCL18) belongs to the chemokine CC family and is predominantly secreted by M2-tumor-associated macrophages. It has been reported to be associated with various diseases and malignancies. Previous studies showed that CCL18 promotes metastasis by activating downstream kinases. However, it remains unknown whether CCL18 regulates post-translational modifications, other than phosphorylation, during tumorigenesis. Here, we demonstrate that CCL18 is up-regulated in non-small cell lung cancer (NSCLC) and is involved in regulating the lysine acetylome in A549 cells. Using the combination of SILAC labeling and high-efficiency acetylation enrichment methods, we identified 1372 lysine acetylation (Kac) sites on 796 proteins in CCL18-treated A549 cells. Among the identified Kac sites, 147 from 126 proteins were down-regulated and seven from five proteins were up-regulated with fold changes more than two and the p-value less than 0.05. Bioinformatics analysis further showed that the proteins with down-regulated acetylation play critical roles in glycolysis, oxidative phosphorylation, tricarboxylic acid cycle, and pentose phosphate pathway in A549 cells. These results suggest that CCL18 may be involved in the development of NSCLC by regulating acetylation of the proteins in many fundamental cellular processes, especially the metabolic reprogramming of tumor cells.