PMID- 24028437
OWN - NLM
STAT- MEDLINE
DCOM- 20150512
LR  - 20220330
IS  - 1442-2050 (Electronic)
IS  - 1120-8694 (Linking)
VI  - 27
IP  - 7
DP  - 2014 Sep-Oct
TI  - Blockage of Nrf2 suppresses the migration and invasion of esophageal squamous 
      cell carcinoma cells in hypoxic microenvironment.
PG  - 685-92
LID - 10.1111/dote.12124 [doi]
AB  - Nuclear factor erythroid-2-related factor 2 (Nrf2) is a critical cell protector 
      by inducing phase two detoxifying and anti-oxidant enzymes in normal cells. But 
      recently, numerous evidence show Nrf2 may play the same beneficial roles toward 
      the cancer cells. Nrf2 is found upexpressed in lots of cancers and promote the 
      proliferation and drug resistance. But studies about the role of Nrf2 in the 
      metastases are few. It has been testified that the tumor cells are under hypoxic 
      conditions. As an important anti-oxidant element, the expression of Nrf2 may be 
      upregulated, which in turn promotes the tumor invasion and metastases in the 
      hypoxic microenvironment. Our team found the expression of Nrf2 correlated with 
      the lymph node metastasis of esophageal squamous cell carcinoma by pathological 
      sections of esophageal carcinoma patients. Further, the mechanism beneath it was 
      studied in this paper. It was hypothesized that the hypoxia microenvironment 
      transformed Nrf2 a friend to a foe. First, Eca-109 cells were treated with 
      different concentration of CoCl2 . Western blot and quantitative reverse 
      transcription-polymerase chain reaction showed that with the increase of the 
      concentration of CoCl2 , the expression levels of Nrf2 and hypoxia-inducible 
      factor-1 (HIF-1) alpha were upregulated simultaneously. By analyzing the data, a 
      significant correlation between Nrf2 and HIF-1 alpha in the protein levels was 
      found. Further, blockage of Nrf2 mediated by shRNA suppressed the expression of 
      HIF-1 alpha, hemeoxygenase-1 (HO-1), and matrix metalloproteinase 2 but enhanced 
      the expression of E-cadherin. In addition, the results of wound healing and 
      invasion assay-verified blockage of Nrf2 suppressed the migration and invasion. 
      So it was suggested that blockage of Nrf2 repressed the migration and invasion of 
      esophageal squamous cell carcinoma cells in the hypoxic microenvironment. HIF-1 
      alpha might be one of the downstream genes of Nrf2 regulated through Nrf2/HO-1 
      axis in the CoCl2 model. Nrf2 inhibition suppressed matrix metalloproteinase 2 
      and enhanced E-cadherin partly through HIF-1 alpha way.
CI  - (c) 2013 Wiley Periodicals, Inc. and the International Society for Diseases of the 
      Esophagus.
FAU - Shen, H
AU  - Shen H
AD  - Department of Thoracic Oncosurgery, First Hospital of Xi'an Jiaotong University, 
      Xi'an, Shaanxi, China; The Third Department of Journal Surgery, First Hospital of 
      Nanchang, Nanchang, Jiangxi, China.
FAU - Yang, Y
AU  - Yang Y
FAU - Xia, S
AU  - Xia S
FAU - Rao, B
AU  - Rao B
FAU - Zhang, J
AU  - Zhang J
FAU - Wang, J
AU  - Wang J
LA  - eng
PT  - Journal Article
DEP - 20130913
PL  - United States
TA  - Dis Esophagus
JT  - Diseases of the esophagus : official journal of the International Society for 
      Diseases of the Esophagus
JID - 8809160
RN  - 0 (Cadherins)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NFE2L2 protein, human)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
RN  - EC 1.14.14.18 (HMOX1 protein, human)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - EC 3.4.24.24 (MMP2 protein, human)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
SB  - IM
MH  - Cadherins/genetics/metabolism
MH  - Carcinoma, Squamous Cell/genetics/metabolism/*pathology
MH  - Cell Line, Tumor
MH  - Cell Movement/*genetics
MH  - Esophageal Neoplasms/genetics/metabolism/*pathology
MH  - Esophageal Squamous Cell Carcinoma
MH  - *Gene Expression Regulation, Neoplastic
MH  - Heme Oxygenase-1/genetics/metabolism
MH  - Humans
MH  - Hypoxia/*metabolism
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/metabolism
MH  - Lymphatic Metastasis
MH  - Matrix Metalloproteinase 2/genetics/metabolism
MH  - NF-E2-Related Factor 2/antagonists & inhibitors/*genetics/metabolism
MH  - Neoplasm Invasiveness/genetics
MH  - RNA, Messenger/*genetics
MH  - RNA, Small Interfering
MH  - *Tumor Microenvironment
MH  - Up-Regulation
OTO - NOTNLM
OT  - ESCC
OT  - Nrf2
OT  - hypoxic microenvironment
OT  - migration and invasion
EDAT- 2013/09/14 06:00
MHDA- 2015/05/13 06:00
CRDT- 2013/09/14 06:00
PHST- 2013/09/14 06:00 [entrez]
PHST- 2013/09/14 06:00 [pubmed]
PHST- 2015/05/13 06:00 [medline]
AID - 10.1111/dote.12124 [doi]
PST - ppublish
SO  - Dis Esophagus. 2014 Sep-Oct;27(7):685-92. doi: 10.1111/dote.12124. Epub 2013 Sep 
      13.