PMID- 25333643
OWN - NLM
STAT- MEDLINE
DCOM- 20150624
LR  - 20220410
IS  - 1791-2431 (Electronic)
IS  - 1021-335X (Linking)
VI  - 32
IP  - 6
DP  - 2014 Dec
TI  - Kruppel-like factor 8 involved in hypoxia promotes the invasion and metastasis of 
      gastric cancer via epithelial to mesenchymal transition.
PG  - 2397-404
LID - 10.3892/or.2014.3495 [doi]
AB  - Previously, we reported that hypoxia was able to induce invasion and metastasis 
      in gastric cancer and that hypoxia-inducible factor-1 (HIF-1) is a key factor 
      involved in this tumor type. Kruppel-like factor 8 (KLF8) as a transcriptional 
      repressor has been suggested as a promoter of tumor metastasis in breast cancer 
      and an inducer of the epithelial‑mesenchymal transition (EMT). KLF8 is also 
      highly expressed in gastric cancer tissues, contributing to poor prognosis. 
      However, the association between KLF8 and HIF-1 in regulating the progression of 
      human gastric cancer in hypoxia is unclear. In the present study, we found that 
      KLF8 was overexpressed in gastric cancer metastatic tissues and cells. 
      Additionally, KLF8 siRNA significantly inhibited SGC7901 cell invasion and 
      migration compared with SGC7901, SGC7901/Scr-si cells. Hypoxia is thus able to 
      induce KLF8 expression and EMT in SGC7901 cells. However, following the 
      examination of changes in cell morphology and epithelial and mesenchymal markers, 
      it was found that KLF8 siRNA and HIF-1 siRNA strongly reversed EMT in cells 
      undergoing hypoxia. Furthermore, hypoxia-induced KLF8 overexpression was 
      attenuated by HIF-1 siRNA. Experiments using luciferase promoter constructs 
      resulted in a marked increase in the activity of cells exposed to hypoxia and 
      decreased activity in cells co-transfected with HIF-1 siRNA. The chromatin 
      immunoprecipitation assay revealed proximal HRE at -133 is the main HIF-1 binding 
      site in the KLF8 promoter. In conclusion, the results demonstrated that KLF8 is 
      actively enhanced by hypoxia and is a novel HIF-1 target. KLF8 is a novel EMT 
      regulating transcription factor that involved in the progression of gastric 
      cancer. The specific anti-EMT drugs in combination with anti-hypoxia are new 
      promising cancer therapies.
FAU - Liu, Na
AU  - Liu N
AD  - Department of Oncology, Tangdu Hospital, Fourth Military Medical University, 
      Xi'an, Shaanxi 710038, P.R. China.
FAU - Wang, Yafang
AU  - Wang Y
AD  - Department of Oncology, Tangdu Hospital, Fourth Military Medical University, 
      Xi'an, Shaanxi 710038, P.R. China.
FAU - Zhou, Yongan
AU  - Zhou Y
AD  - Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical 
      University, Xi'an, Shaanxi 710038, P.R. China.
FAU - Pang, Hailin
AU  - Pang H
AD  - Department of Oncology, Tangdu Hospital, Fourth Military Medical University, 
      Xi'an, Shaanxi 710038, P.R. China.
FAU - Zhou, Jing
AU  - Zhou J
AD  - Department of Oncology, Tangdu Hospital, Fourth Military Medical University, 
      Xi'an, Shaanxi 710038, P.R. China.
FAU - Qian, Pei
AU  - Qian P
AD  - Department of Oncology, Tangdu Hospital, Fourth Military Medical University, 
      Xi'an, Shaanxi 710038, P.R. China.
FAU - Liu, Lili
AU  - Liu L
AD  - Department of Oncology, Tangdu Hospital, Fourth Military Medical University, 
      Xi'an, Shaanxi 710038, P.R. China.
FAU - Zhang, Helong
AU  - Zhang H
AD  - Department of Oncology, Tangdu Hospital, Fourth Military Medical University, 
      Xi'an, Shaanxi 710038, P.R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140918
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (KLF8 protein, human)
RN  - 0 (Kruppel-Like Transcription Factors)
RN  - 0 (Repressor Proteins)
SB  - IM
MH  - Adenocarcinoma/*metabolism/secondary
MH  - Animals
MH  - Binding Sites
MH  - Cell Hypoxia
MH  - *Epithelial-Mesenchymal Transition
MH  - Gene Expression
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/physiology
MH  - Kruppel-Like Transcription Factors
MH  - Mice, Nude
MH  - Neoplasm Invasiveness
MH  - Neoplasm Transplantation
MH  - Promoter Regions, Genetic
MH  - Repressor Proteins/*physiology
MH  - Stomach Neoplasms/*metabolism/pathology
EDAT- 2014/10/22 06:00
MHDA- 2015/06/25 06:00
CRDT- 2014/10/22 06:00
PHST- 2014/04/14 00:00 [received]
PHST- 2014/07/17 00:00 [accepted]
PHST- 2014/10/22 06:00 [entrez]
PHST- 2014/10/22 06:00 [pubmed]
PHST- 2015/06/25 06:00 [medline]
AID - 10.3892/or.2014.3495 [doi]
PST - ppublish
SO  - Oncol Rep. 2014 Dec;32(6):2397-404. doi: 10.3892/or.2014.3495. Epub 2014 Sep 18.