PMID- 23233904
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20121213
LR  - 20211021
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 2
DP  - 2012
TI  - VDAC1: from structure to cancer therapy.
PG  - 164
LID - 10.3389/fonc.2012.00164 [doi]
LID - 164
AB  - Here, we review current evidence pointing to the function of VDAC1 in cell life 
      and death, and highlight these functions in relation to cancer. Found at the 
      outer mitochondrial membrane, VDAC1 assumes a crucial position in the cell, 
      controlling the metabolic cross-talk between mitochondria and the rest of the 
      cell. Moreover, its location at the boundary between the mitochondria and the 
      cytosol enables VDAC1 to interact with proteins that mediate and regulate the 
      integration of mitochondrial functions with other cellular activities. As a 
      metabolite transporter, VDAC1 contributes to the metabolic phenotype of cancer 
      cells. This is reflected by VDAC1 over-expression in many cancer types, and by 
      inhibition of tumor development upon silencing VDAC1 expression. Along with 
      regulating cellular energy production and metabolism, VDAC1 is also a key protein 
      in mitochondria-mediated apoptosis, participating in the release of apoptotic 
      proteins and interacting with anti-apoptotic proteins. The involvement of VDAC1 
      in the release of apoptotic proteins located in the inter-membranal space is 
      discussed, as is VDAC1 oligomerization as an important step in apoptosis 
      induction. VDAC also serves as an anchor point for mitochondria-interacting 
      proteins, some of which are also highly expressed in many cancers, such as 
      hexokinase (HK), Bcl2, and Bcl-xL. By binding to VDAC, HK provides both metabolic 
      benefit and apoptosis-suppressive capacity that offers the cell a proliferative 
      advantage and increases its resistance to chemotherapy. VDAC1-based peptides that 
      bind specifically to HK, Bcl2, or Bcl-xL abolished the cell's abilities to bypass 
      the apoptotic pathway. Moreover, these peptides promote cell death in a panel of 
      genetically characterized cell lines derived from different human cancers. These 
      and other functions point to VDAC1 as a rational target for the development of a 
      new generation of therapeutics.
FAU - Shoshan-Barmatz, Varda
AU  - Shoshan-Barmatz V
AD  - Department of Life Sciences, Ben-Gurion University of the Negev Beer-Sheva, 
      Israel ; The National Institute for Biotechnology in the Negev, Ben-Gurion 
      University of the Negev Beer-Sheva, Israel.
FAU - Mizrachi, Dario
AU  - Mizrachi D
LA  - eng
PT  - Journal Article
DEP - 20121129
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC3516065
OTO - NOTNLM
OT  - VDAC protein
OT  - anti-apoptotic Bcl-2
OT  - apoptosis
OT  - cancer metabolism
OT  - hexokinase
OT  - mitochondrial porin
EDAT- 2012/12/13 06:00
MHDA- 2012/12/13 06:01
PMCR- 2012/01/01
CRDT- 2012/12/13 06:00
PHST- 2012/07/29 00:00 [received]
PHST- 2012/10/24 00:00 [accepted]
PHST- 2012/12/13 06:00 [entrez]
PHST- 2012/12/13 06:00 [pubmed]
PHST- 2012/12/13 06:01 [medline]
PHST- 2012/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2012.00164 [doi]
PST - epublish
SO  - Front Oncol. 2012 Nov 29;2:164. doi: 10.3389/fonc.2012.00164. eCollection 2012.