PMID- 20381449
OWN - NLM
STAT- MEDLINE
DCOM- 20110110
LR  - 20211020
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1797
IP  - 6-7
DP  - 2010 Jun-Jul
TI  - The pivotal roles of mitochondria in cancer: Warburg and beyond and encouraging 
      prospects for effective therapies.
PG  - 1225-30
LID - 10.1016/j.bbabio.2010.03.025 [doi]
AB  - Tumors usurp established metabolic steps used by normal tissues for glucose 
      utilization and ATP production that rely heavily on mitochondria and employ a 
      route that, although involving mitochondria, includes a much greater dependency 
      on glycolysis. First described by Otto Warburg almost nine decades ago [1], this 
      aberrant phenotype becomes more pronounced with increased tumor malignancy [2]. 
      Thus, while maintaining their capacity for respiration, tumors "turn more 
      parasitic" by enhancing their ability to scavenge glucose from their 
      surroundings. With excess glucose at hand, tumors shunt their metabolic flux more 
      toward glycolysis than do their normal cells of origin, a strategy that allows 
      for their survival when oxygen is limiting while providing them a mechanism to 
      poison their extra-cellular environment with acid, thus paving the way for 
      invasion and metastasis. Significantly, tumors harness a crucial enzyme to 
      regulate and support this destructive path--to entrap and channel glucose toward 
      glycolysis. This enzyme is an isoform of hexokinase, referred to as hexokinase 
      type II, and also in abbreviated form as HK-2 or HK II. Due to many-faceted 
      molecular features at genetic, epigenetic, transcriptional, and enzymatic levels, 
      including sub-cellular localization to mitochondria, HK-2 facilitates and 
      promotes the high glycolytic tumor phenotype [3]. Thus, HK-2 represents a pivotal 
      model gene or enzyme that tumors "select for" during tumorigenesis in order to 
      facilitate their destructive path. In this review, we examine the roles played by 
      mitochondrial bound HK-2 within the context of the highly choreographed metabolic 
      roulette of malignant tumors. Recent studies that outline how the aberrant 
      glycolytic flux can be subverted toward a more "normal" metabolic phenotype, and 
      how the glycolytic flux affects the tumor microenvironment to facilitate tumor 
      dissemination are also described, including how these very features can be 
      harnessed in new metabolic targeting strategies to selectively debilitate tumors.
CI  - Copyright (c) 2010 Elsevier B.V. All rights reserved.
FAU - Mathupala, Saroj P
AU  - Mathupala SP
AD  - Department of Neurological Surgery and Karmanos Cancer Institute, Wayne State 
      University School of Medicine, Detroit, MI 48201, USA.
FAU - Ko, Young H
AU  - Ko YH
FAU - Pedersen, Peter L
AU  - Pedersen PL
LA  - eng
GR  - R01 CA010951-40/CA/NCI NIH HHS/United States
GR  - R01 CA080118-05/CA/NCI NIH HHS/United States
GR  - R01 CA116257/CA/NCI NIH HHS/United States
GR  - R01 CA116257-05/CA/NCI NIH HHS/United States
GR  - R01 CA010951/CA/NCI NIH HHS/United States
PT  - Historical Article
PT  - Journal Article
PT  - Review
DEP - 20100408
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Monocarboxylic Acid Transporters)
RN  - 0 (Proton Pumps)
RN  - 33X04XA5AT (Lactic Acid)
RN  - EC 2.7.1.1 (Hexokinase)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Glucose/metabolism
MH  - Glycolysis
MH  - Hexokinase/genetics/metabolism
MH  - History, 20th Century
MH  - History, 21st Century
MH  - Humans
MH  - Lactic Acid
MH  - Mitochondria/*metabolism
MH  - Models, Biological
MH  - Monocarboxylic Acid Transporters/metabolism
MH  - Neoplasms/genetics/*metabolism/pathology/*therapy
MH  - Proton Pumps/metabolism
MH  - Research/history
PMC - PMC2890051
MID - NIHMS196386
EDAT- 2010/04/13 06:00
MHDA- 2011/01/11 06:00
PMCR- 2011/06/01
CRDT- 2010/04/13 06:00
PHST- 2009/12/16 00:00 [received]
PHST- 2010/03/03 00:00 [revised]
PHST- 2010/03/30 00:00 [accepted]
PHST- 2010/04/13 06:00 [entrez]
PHST- 2010/04/13 06:00 [pubmed]
PHST- 2011/01/11 06:00 [medline]
PHST- 2011/06/01 00:00 [pmc-release]
AID - S0005-2728(10)00131-3 [pii]
AID - 10.1016/j.bbabio.2010.03.025 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2010 Jun-Jul;1797(6-7):1225-30. doi: 
      10.1016/j.bbabio.2010.03.025. Epub 2010 Apr 8.