PMID- 28284859
OWN - NLM
STAT- MEDLINE
DCOM- 20170601
LR  - 20180104
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Linking)
VI  - 322
DP  - 2017 May 1
TI  - Molecular mechanisms of 3,3'4,4',5-pentachlorobiphenyl-induced 
      epithelial-mesenchymal transition in human hepatocellular carcinoma cells.
PG  - 75-88
LID - S0041-008X(17)30101-1 [pii]
LID - 10.1016/j.taap.2017.03.003 [doi]
AB  - 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 48h, 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.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Song, Li
AU  - Song L
AD  - Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular 
      Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, 
      China.
FAU - Guo, Linlin
AU  - Guo L
AD  - Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular 
      Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, 
      China.
FAU - Li, Zhuoyu
AU  - Li Z
AD  - Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular 
      Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, 
      China; College of Life Science, Zhejiang Chinese Medical University, Hangzhou 
      310053, China. Electronic address: lzy@sxu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170308
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Estrogen Antagonists)
RN  - 0 (Reactive Oxygen Species)
RN  - DFC2HB4I0K (Polychlorinated Biphenyls)
RN  - TSH69IA9XF (3,4,5,3',4'-pentachlorobiphenyl)
SB  - IM
MH  - Carcinoma, Hepatocellular/*metabolism
MH  - Cell Adhesion/drug effects/physiology
MH  - Dose-Response Relationship, Drug
MH  - Epithelial-Mesenchymal Transition/*drug effects/*physiology
MH  - Estrogen Antagonists/toxicity
MH  - Humans
MH  - Liver Neoplasms/*metabolism
MH  - Polychlorinated Biphenyls/*toxicity
MH  - Reactive Oxygen Species/metabolism
MH  - Tumor Cells, Cultured
OTO - NOTNLM
OT  - 3,3'4,4',5-Pentachlorobiphenyl
OT  - Epithelial-mesenchymal transition
OT  - Hepatocellular carcinoma
OT  - PKM2
OT  - STAT3/Snail1 pathway
EDAT- 2017/03/13 06:00
MHDA- 2017/06/02 06:00
CRDT- 2017/03/13 06:00
PHST- 2016/11/01 00:00 [received]
PHST- 2017/02/28 00:00 [revised]
PHST- 2017/03/04 00:00 [accepted]
PHST- 2017/03/13 06:00 [pubmed]
PHST- 2017/06/02 06:00 [medline]
PHST- 2017/03/13 06:00 [entrez]
AID - S0041-008X(17)30101-1 [pii]
AID - 10.1016/j.taap.2017.03.003 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2017 May 1;322:75-88. doi: 10.1016/j.taap.2017.03.003. 
      Epub 2017 Mar 8.