PMID- 23301832
OWN - NLM
STAT- MEDLINE
DCOM- 20131113
LR  - 20211021
IS  - 1582-4934 (Electronic)
IS  - 1582-1838 (Print)
IS  - 1582-1838 (Linking)
VI  - 17
IP  - 1
DP  - 2013 Jan
TI  - Hypoxia-inducing factors as master regulators of stemness properties and altered 
      metabolism of cancer- and metastasis-initiating cells.
PG  - 30-54
LID - 10.1111/jcmm.12004 [doi]
AB  - Accumulating lines of experimental evidence have revealed that hypoxia-inducible 
      factors, HIF-1alpha and HIF-2alpha, are key regulators of the adaptation of cancer- and 
      metastasis-initiating cells and their differentiated progenies to oxygen and 
      nutrient deprivation during cancer progression under normoxic and hypoxic 
      conditions. Particularly, the sustained stimulation of epidermal growth factor 
      receptor (EGFR), insulin-like growth factor-1 receptor (IGF-1R), stem cell factor 
      (SCF) receptor KIT, transforming growth factor-beta receptors (TGF-betaRs) and Notch 
      and their downstream signalling elements such as phosphatidylinositol 3'-kinase 
      (PI3K)/Akt/molecular target of rapamycin (mTOR) may lead to an enhanced activity 
      of HIFs. Moreover, the up-regulation of HIFs in cancer cells may also occur in 
      the hypoxic intratumoral regions formed within primary and secondary neoplasms as 
      well as in leukaemic cells and metastatic prostate and breast cancer cells homing 
      in the hypoxic endosteal niche of bone marrow. The activated HIFs may induce the 
      expression of numerous gene products such as induced pluripotency-associated 
      transcription factors (Oct-3/4, Nanog and Sox-2), glycolysis- and 
      epithelial-mesenchymal transition (EMT) programme-associated molecules, including 
      CXC chemokine receptor 4 (CXCR4), snail and twist, microRNAs and angiogenic 
      factors such as vascular endothelial growth factor (VEGF). These gene products in 
      turn can play critical roles for high self-renewal ability, survival, altered 
      energy metabolism, invasion and metastases of cancer cells, angiogenic switch and 
      treatment resistance. Consequently, the targeting of HIF signalling network and 
      altered metabolic pathways represents new promising strategies to eradicate the 
      total mass of cancer cells and improve the efficacy of current therapies against 
      aggressive and metastatic cancers and prevent disease relapse.
CI  - (c) 2012 The Authors. Published by Foundation for Cellular and Molecular 
      Medicine/Blackwell Publishing Ltd. This is an open access article under the terms 
      of the Creative Commons Attribution License, which permits use, distribution and 
      reproduction in any medium, provided the original work is properly cited.
FAU - Mimeault, Murielle
AU  - Mimeault M
AD  - Department of Biochemistry and Molecular Biology, College of Medicine, Eppley 
      Cancer Institute, University of Nebraska Medical Center, Omaha, NE 68198-5870, 
      USA. mmimeault@unmc.edu
FAU - Batra, Surinder K
AU  - Batra SK
LA  - eng
GR  - U54 CA163120/CA/NCI NIH HHS/United States
GR  - U01 CA111294/CA/NCI NIH HHS/United States
GR  - R01 CA138791/CA/NCI NIH HHS/United States
GR  - P50 CA127297/CA/NCI NIH HHS/United States
GR  - R01CA138791/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20130110
PL  - England
TA  - J Cell Mol Med
JT  - Journal of cellular and molecular medicine
JID - 101083777
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Transcription Factors)
RN  - 1B37H0967P (endothelial PAS domain-containing protein 1)
SB  - IM
MH  - Antineoplastic Agents/pharmacology
MH  - Apoptosis
MH  - Basic Helix-Loop-Helix Transcription Factors/*genetics/metabolism
MH  - Cell Transformation, Neoplastic/drug effects
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Hypoxia/drug therapy/*genetics/metabolism/pathology
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*genetics/metabolism
MH  - Intercellular Signaling Peptides and Proteins/genetics/metabolism
MH  - Molecular Targeted Therapy
MH  - Neoplasm Metastasis
MH  - Neoplasms/drug therapy/*genetics/metabolism/pathology
MH  - Neoplastic Stem Cells/drug effects/*metabolism/pathology
MH  - Signal Transduction
MH  - Transcription Factors/genetics/metabolism
PMC - PMC3560853
MID - NIHMS435635
EDAT- 2013/01/11 06:00
MHDA- 2013/11/14 06:00
PMCR- 2013/01/01
CRDT- 2013/01/11 06:00
PHST- 2012/06/20 00:00 [received]
PHST- 2012/11/20 00:00 [accepted]
PHST- 2013/01/11 06:00 [entrez]
PHST- 2013/01/11 06:00 [pubmed]
PHST- 2013/11/14 06:00 [medline]
PHST- 2013/01/01 00:00 [pmc-release]
AID - 10.1111/jcmm.12004 [doi]
PST - ppublish
SO  - J Cell Mol Med. 2013 Jan;17(1):30-54. doi: 10.1111/jcmm.12004. Epub 2013 Jan 10.