Nonylphenol Promoted Epithelial–Mesenchymal Transition in Colorectal Cancer Cells by Upregulating the Expression of Regulator of Cell Cycle

Abstract

Nonylphenol (NP) is a widely used chemical, which has been considered a kind of endocrine-disrupting chemical and is involved in the occurrence and development of many types of cancers. Our recent studies demonstrated that NP exposure is related to colorectal cancer (CRC) progression. In this study, we also found epithelial–mesenchymal transition (EMT) promoted by NP treatment in CRC cells. However, the mechanism of NP on tumor metastasis is still unclear. In this study, we focused on the effect of the regulator of cell cycle (RGCC) induced by NP treatment. The cancer genome atlas (TCGA) analysis suggested that the expression of RGCC increased in CRC tissues, and our clinical samples showed that the expression of RGCC in tumor tissues is positively correlated with the serum level of NP in CRC patients. Further studies revealed that overexpression of RGCC could enhance the NP-induced EMT process in CRC cells and activate ERK signaling pathways. Inhibiting ERK signaling by ERK inhibitors or the knockdown of RGCC could attenuate the NP-induced EMT process. In addition, both RGCC overexpression and NP treatment could activate ERK pathways and attenuate the effect of ERK inhibitors on the EMT process in CRC cells. Altogether, this study demonstrated that NP could induce cell invasion and migration by increasing the expression of RGCC to enhance the EMT process, which might be through the activation of ERK signaling pathways. This finding supported a potential target for studying NP exposure-related colorectal cancers.

Comprehensive Toxicological Assessment of Halobenzoquinones in Drinking Water at Environmentally Relevant Concentration

“…Previous toxicity studies have suggested that activation of the ERK pathway is involved in the EMT process, and this was proven by numerous pollutants, such as bisphenol A, dioxin, and nonylphenol. − To explore whether the ERK pathway contributes to the HBQ-induced EMT process, we examined the expression of ERK and p-ERK through Western blot analysis. As shown in Figure c, 2,5-DBBQ and 2,6-DCBQ exposure significantly increased the ratio of p-ERK to ERK in THLE-2 cells, while 2,6-DBBQ and TriCBQ treatments had only slight influences.…”