Plasticizers are considered as environmental pollution released from medical devices and increased potential oncogenic risks in clinical
therapy. Our previous studies have shown that long-term exposure to di-ethylhexyl
phthalate (
DEHP)/
mono-ethylhexyl phthalate (
MEHP) promotes chemotherapeutic drug resistance in
colorectal cancer. In this study, we investigated the alteration of glycosylation in
colorectal cancer following long-term
plasticizers exposure. First, we determined the profiles of cell surface N-glycomes by using mass spectrometry and found out the alterations of α2,8-linkages
glycans. Next, we analyzed the correlation between serum
DEHP/
MEHP levels and ST8SIA6 expression from matched tissues in total 110
colorectal cancer patients. Moreover, clinical specimens and TCGA database were used to analyze the expression of ST8SIA6 in advanced stage of
cancer. Finally, we showed that ST8SIA6 regulated stemness in vitro and in vivo. Our results revealed long-term
DEHP/
MEHP exposure significantly caused
cancer patients with poorer survival outcome and attenuated the expression of ST8SIA6 in
cancer cells and tissue samples. As expected, silencing of ST8SIA6 promoted
cancer stemness and tumorigenicity by upregulating stemness-associated
proteins. In addition, the cell viability assay showed enhanced drug resistance in ST8SIA6 silencing cells treated with
irinotecan. Besides, ST8SIA6 was downregulated in the advanced stage and positively correlated with
tumor recurrence in
colorectal cancer. Our results imply that ST8SIA6 potentially plays an important role in oncogenic effects with long-term phthalates exposure.