PMID- 27543779
OWN - NLM
STAT- MEDLINE
DCOM- 20170912
LR  - 20180130
IS  - 1460-2180 (Electronic)
IS  - 0143-3334 (Linking)
VI  - 37
IP  - 11
DP  - 2016 Nov 1
TI  - Downregulation of AIF by HIF-1 contributes to hypoxia-induced 
      epithelial-mesenchymal transition of colon cancer.
PG  - 1079-1088
LID - 10.1093/carcin/bgw089 [doi]
AB  - Recently, we have reported that apoptosis-inducing factor (AIF) regulates the 
      epithelial-mesenchymal transition (EMT) process of cancers, but the mechanisms 
      underlying the regulation of AIF expression in cancers remain greatly unknown. 
      Here, we report that hypoxia inversely correlates with the expression of AIF in 
      tumor tissues from a cohort of colon cancer patients and inhibits AIF expression 
      in multiple colon cancer cell lines. This inhibition is mediated by 
      hypoxia-inducible factor-1 (HIF-1), which transcriptionally represses AIF through 
      direct binding to the hypoxia-response element in AIF promoter as revealed by 
      luciferase reporter and chromatin immunoprecipitation assays. We also show that 
      downregulation of AIF contributes to hypoxia-induced EMT as overexpression or 
      silencing of AIF partially reverses or potentiates the EMT program initiated by 
      hypoxic treatment. Mechanistic study reveals that downregulation of AIF by 
      hypoxia causes oxidative inactivation of the lipid phosphatase activity of 
      phosphatase and tensin homolog on chromosome 10 (PTEN), with ensuing activation 
      of Akt kinase, phosphorylation of the Akt substrate GSK-3beta and activation of 
      WNT/beta-catenin signaling in colon cancer cells. These results identify AIF as a 
      novel target gene of HIF-1 and reveal the role of AIF downregulation in 
      hypoxia-induced EMT.
CI  - (c) The Author 2016. Published by Oxford University Press. All rights reserved. For 
      Permissions, please email: journals.permissions@oup.com.
FAU - Xiong, Zhong
AU  - Xiong Z
AD  - Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of 
      Education, Department of Pathophysiology, Ruijin Hospital, Shanghai Jiao Tong 
      University School of Medicine (SJTU-SM) , Shanghai 200025 , China and.
FAU - Guo, Meng
AU  - Guo M
AD  - Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of 
      Education, Department of Pathophysiology, Ruijin Hospital, Shanghai Jiao Tong 
      University School of Medicine (SJTU-SM) , Shanghai 200025 , China and.
FAU - Yu, Yun
AU  - Yu Y
AD  - Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of 
      Education, Department of Pathophysiology, Ruijin Hospital, Shanghai Jiao Tong 
      University School of Medicine (SJTU-SM) , Shanghai 200025 , China and.
FAU - Zhang, Fei-Fei
AU  - Zhang FF
AD  - Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of 
      Education, Department of Pathophysiology, Ruijin Hospital, Shanghai Jiao Tong 
      University School of Medicine (SJTU-SM) , Shanghai 200025 , China and.
FAU - Ge, Meng-Kai
AU  - Ge MK
AD  - Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of 
      Education, Department of Pathophysiology, Ruijin Hospital, Shanghai Jiao Tong 
      University School of Medicine (SJTU-SM) , Shanghai 200025 , China and.
FAU - Chen, Guo-Qiang
AU  - Chen GQ
AD  - Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of 
      Education, Department of Pathophysiology, Ruijin Hospital, Shanghai Jiao Tong 
      University School of Medicine (SJTU-SM), Shanghai 200025, China and.
AD  - Institute of Health Science, Shanghai Institutes for Biological Sciences of 
      Chinese Academy of Sciences (SJTU-SM), Shanghai 200025, China.
FAU - Shen, Shao-Ming
AU  - Shen SM
AD  - Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of 
      Education, Department of Pathophysiology, Ruijin Hospital, Shanghai Jiao Tong 
      University School of Medicine (SJTU-SM) , Shanghai 200025 , China and.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Carcinogenesis
JT  - Carcinogenesis
JID - 8008055
RN  - 0 (AIFM1 protein, human)
RN  - 0 (Apoptosis Inducing Factor)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (PTEN protein, human)
SB  - IM
MH  - Animals
MH  - Apoptosis Inducing Factor/*genetics/metabolism
MH  - Base Sequence
MH  - Binding Sites
MH  - Cell Hypoxia
MH  - Cell Line, Tumor
MH  - Colonic Neoplasms/*metabolism/pathology
MH  - Down-Regulation
MH  - *Epithelial-Mesenchymal Transition
MH  - Gene Expression
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*physiology
MH  - Mice
MH  - Oxidation-Reduction
MH  - PTEN Phosphohydrolase/metabolism
MH  - Promoter Regions, Genetic
MH  - Wnt Signaling Pathway
EDAT- 2016/08/21 06:00
MHDA- 2017/09/13 06:00
CRDT- 2016/08/21 06:00
PHST- 2015/12/31 00:00 [received]
PHST- 2016/08/19 00:00 [accepted]
PHST- 2016/08/21 06:00 [pubmed]
PHST- 2017/09/13 06:00 [medline]
PHST- 2016/08/21 06:00 [entrez]
AID - bgw089 [pii]
AID - 10.1093/carcin/bgw089 [doi]
PST - ppublish
SO  - Carcinogenesis. 2016 Nov 1;37(11):1079-1088. doi: 10.1093/carcin/bgw089.