Dynamic analysis of proteomic alterations in response to N-linked glycosylation inhibition in a drug-resistant ovarian carcinoma cell line.

Glycosylation inhibition can improve the efficacy of antitumor drugs and enhance the apoptosis of cancer cells, thus holding great potential for cancer treatment. Inhibition of N-glycosylation induces endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), and eventually triggers ER stress-related apoptosis. Unfortunately, the detailed timeline of these cell responses and protein expression alterations related to N-glycosylation inhibition is not explicit yet, and the pathways involved in different stages of N-glycosylation inhibition still need to be characterized. In this study, the dynamic proteome alterations related to N-glycosylation inhibition were investigated by further analyzing our previously published quantitative proteomics data from tunicamycin (TM)-treated ovarian carcinoma (OVCAR-3) cells. The results revealed that N-glycosylation inhibition not only directly affects the expression of glycosylated proteins but also alters an extended scale of proteins. Functional annotation of these altered proteins demonstrated that proteins related to ER stress start changing within 6 h, followed by UPR within 24 h, and eventually ER stress-related apoptosis is triggered after 48 h, indicating the conversion of cellular response from positive to negative. The dynamic proteome data presented here provide important information for better understanding of the significance of N-glycosylation to cell survival and TM-related cancer treatment.