PMID- 23597945
OWN - NLM
STAT- MEDLINE
DCOM- 20140122
LR  - 20161125
IS  - 2213-3941 (Electronic)
IS  - 0003-4266 (Linking)
VI  - 74
IP  - 2
DP  - 2013 May
TI  - Tumor hypoxia and metabolism -- towards novel anticancer approaches.
PG  - 111-4
LID - S0003-4266(13)00022-X [pii]
LID - 10.1016/j.ando.2013.02.004 [doi]
AB  - The transcription factor hypoxia-inducible factor-1 (HIF-1) facilitates the 
      induction of enzymes necessary for regulation of biological processes required 
      for cell survival and the acquisition of an aggressive and invasive phenotype, 
      such as regulation of the intracellular pH (pHi), anaerobic glycolysis, 
      angiogenesis, migration/invasion... In this presentation, we will highlight some 
      of the HIF-1-induced gene products - carbonic anhydrases IX and XII (CAs) and 
      monocarboxylate transporters (MCTs) - which regulate the pHi by controlling 
      export of metabolically-generated acids (carbonic and lactic acids). We reported 
      that targeting these pHi-regulated processes through inhibition of either 
      HIF-1-induced CAIX/CAXII or HIF-1-induced MCT4, MCT1 or Basigin/EMMPRIN/CD147 
      chaperone of MCTs, severely restricts glycolysis-generated ATP levels and tumor 
      growth. In addition, we demonstrated that the Myc/HIF-1-targeted 
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH) catalyzing a key step producing 
      the NADH cofactor, activates the Akt pathway, thereby upregulating expression of 
      the anti-apoptotic Bcl-xL. As a consequence, high expression of GAPDH contributes 
      to tumor aggressiveness, in particular in the context Myc-driven B lymphomas. We 
      propose that membrane-bound carbonic anhydrases (CAIX, CAXII), monocarboxylate 
      transporters/chaperon Basigin (Myc-induced MCT1 and HIF-induced-MCT4) and GAPDH 
      that are associated with exacerbated tumor metabolism, represent new potential 
      targets for anticancer therapy.
CI  - Copyright (c) 2013. Published by Elsevier Masson SAS.
FAU - Chiche, Johanna
AU  - Chiche J
AD  - Unite 1065, equipe << controle metabolique des morts cellulaires >>, Institut 
      national de la sante et de la recherche medicale, centre mediterraneen de 
      medecine moleculaire (C3M), 06204 Nice, France. chiche@unice.fr
FAU - Ricci, Jean-Ehrland
AU  - Ricci JE
FAU - Pouyssegur, Jacques
AU  - Pouyssegur J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20130415
PL  - France
TA  - Ann Endocrinol (Paris)
JT  - Annales d'endocrinologie
JID - 0116744
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Drugs, Investigational)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/chemical synthesis/*therapeutic use
MH  - Drugs, Investigational/therapeutic use
MH  - Glucose/metabolism
MH  - Humans
MH  - Hypoxia/drug therapy/genetics/*metabolism
MH  - Hypoxia-Inducible Factor 1/genetics/physiology
MH  - *Molecular Targeted Therapy
MH  - Neoplasms/*drug therapy/genetics/*metabolism
MH  - Signal Transduction/genetics/physiology
EDAT- 2013/04/20 06:00
MHDA- 2014/01/23 06:00
CRDT- 2013/04/20 06:00
PHST- 2013/04/20 06:00 [entrez]
PHST- 2013/04/20 06:00 [pubmed]
PHST- 2014/01/23 06:00 [medline]
AID - S0003-4266(13)00022-X [pii]
AID - 10.1016/j.ando.2013.02.004 [doi]
PST - ppublish
SO  - Ann Endocrinol (Paris). 2013 May;74(2):111-4. doi: 10.1016/j.ando.2013.02.004. 
      Epub 2013 Apr 15.