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Title: Molecular mechanisms of 3,3′4,4′,5-pentachlorobiphenyl-induced epithelial-mesenchymal transition in human hepatocellular carcinoma cells

Abstract

Polychlorinated biphenyls (PCBs) are classic persistent organic pollutants (POPs). Many studies have found a positive association between the progression of hepatocellular carcinoma (HCC) and PCBs exposure. However, the influence of PCBs on epithelial-mesenchymal transition (EMT) of HCC remains to be unclear. In this study, we explored the effect of PCB126 on EMT in HCC cells and its underlying mechanisms. The data showed that PCB126, exposing both Bel-7402 and SMMC-7721 cells for 48 h, promoted EMT that was demonstrated by E-cadherin repression, up-regulation of N-cadherin and vimentin, and morphological alteration. We found that signal transducer and activator of transcription 3 (STAT3)/Snail1 signaling was activated after PCB126 exposure, and the addition of STAT3 inhibitor WP1066 blocked PCB126-induced down-regulation of E-cadherin as well as up-regulation of N-cadherin and vimentin. Moreover, PCB126 exposure increased pyruvate kinase M2 (PKM2) expression and its nuclear translocation, whereas treatment with PKM2 shRNA suppressed the activation of STAT3/Snail1 signaling and the alternation of EMT-related molecules (E-cadherin, N-cadherin and vimentin). Furthermore, this study indicated estrogen receptor (ER) and aryl hydrocarbon receptor (AhR) were involved in PCB126-induced effects on PKM2, STAT3/Snail1 signaling and EMT by according treatment using ER inhibitor ICI and AhR shRNA. Notably, PCB126-increased reactive oxygen species (ROS) productionmore » via AhR is associated with activation of PKM2/STAT3/Snail1 cascades and contributes to EMT. Taken together, these results indicated that PCB126 promotes EMT process of HCC cells via PKM2/STAT3/Snail1 signaling which is mediated by ER and AhR. - Highlights: • PCB126 promotes epithelial-mesenchymal transition of HCC cells. • PCB126 regulates EMT through the activation of STAT3/Snail1 signaling. • PKM2 is responsible for PCB126-induced activation of STAT3/Snail1 signaling. • AhR-induced ROS generation regulates PKM2/STAT3/Snail1 signaling. • PCB126-induced EMT is mediated by ER and AhR.« less

Authors:
;  [1];  [1]
  1. Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006 (China)
Publication Date:
OSTI Identifier:
22690966
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 322; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ESTROGENS; HEPATOMAS; PHOSPHOTRANSFERASES; POLLUTANTS; POLYCHLORINATED BIPHENYLS; RECEPTORS; TRANSCRIPTION; TRANSDUCERS

Citation Formats

Song, Li, Guo, Linlin, Li, Zhuoyu, and College of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053. Molecular mechanisms of 3,3′4,4′,5-pentachlorobiphenyl-induced epithelial-mesenchymal transition in human hepatocellular carcinoma cells. United States: N. p., 2017. Web. doi:10.1016/J.TAAP.2017.03.003.
Song, Li, Guo, Linlin, Li, Zhuoyu, & College of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053. Molecular mechanisms of 3,3′4,4′,5-pentachlorobiphenyl-induced epithelial-mesenchymal transition in human hepatocellular carcinoma cells. United States. https://doi.org/10.1016/J.TAAP.2017.03.003
Song, Li, Guo, Linlin, Li, Zhuoyu, and College of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053. 2017. "Molecular mechanisms of 3,3′4,4′,5-pentachlorobiphenyl-induced epithelial-mesenchymal transition in human hepatocellular carcinoma cells". United States. https://doi.org/10.1016/J.TAAP.2017.03.003.
@article{osti_22690966,
title = {Molecular mechanisms of 3,3′4,4′,5-pentachlorobiphenyl-induced epithelial-mesenchymal transition in human hepatocellular carcinoma cells},
author = {Song, Li and Guo, Linlin and Li, Zhuoyu and College of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053},
abstractNote = {Polychlorinated biphenyls (PCBs) are classic persistent organic pollutants (POPs). Many studies have found a positive association between the progression of hepatocellular carcinoma (HCC) and PCBs exposure. However, the influence of PCBs on epithelial-mesenchymal transition (EMT) of HCC remains to be unclear. In this study, we explored the effect of PCB126 on EMT in HCC cells and its underlying mechanisms. The data showed that PCB126, exposing both Bel-7402 and SMMC-7721 cells for 48 h, promoted EMT that was demonstrated by E-cadherin repression, up-regulation of N-cadherin and vimentin, and morphological alteration. We found that signal transducer and activator of transcription 3 (STAT3)/Snail1 signaling was activated after PCB126 exposure, and the addition of STAT3 inhibitor WP1066 blocked PCB126-induced down-regulation of E-cadherin as well as up-regulation of N-cadherin and vimentin. Moreover, PCB126 exposure increased pyruvate kinase M2 (PKM2) expression and its nuclear translocation, whereas treatment with PKM2 shRNA suppressed the activation of STAT3/Snail1 signaling and the alternation of EMT-related molecules (E-cadherin, N-cadherin and vimentin). Furthermore, this study indicated estrogen receptor (ER) and aryl hydrocarbon receptor (AhR) were involved in PCB126-induced effects on PKM2, STAT3/Snail1 signaling and EMT by according treatment using ER inhibitor ICI and AhR shRNA. Notably, PCB126-increased reactive oxygen species (ROS) production via AhR is associated with activation of PKM2/STAT3/Snail1 cascades and contributes to EMT. Taken together, these results indicated that PCB126 promotes EMT process of HCC cells via PKM2/STAT3/Snail1 signaling which is mediated by ER and AhR. - Highlights: • PCB126 promotes epithelial-mesenchymal transition of HCC cells. • PCB126 regulates EMT through the activation of STAT3/Snail1 signaling. • PKM2 is responsible for PCB126-induced activation of STAT3/Snail1 signaling. • AhR-induced ROS generation regulates PKM2/STAT3/Snail1 signaling. • PCB126-induced EMT is mediated by ER and AhR.},
doi = {10.1016/J.TAAP.2017.03.003},
url = {https://www.osti.gov/biblio/22690966}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = ,
volume = 322,
place = {United States},
year = {Mon May 01 00:00:00 EDT 2017},
month = {Mon May 01 00:00:00 EDT 2017}
}