PMID- 28824871
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 7
DP  - 2017
TI  - Voltage-Dependent Anion Channel 1 As an Emerging Drug Target for Novel 
      Anti-Cancer Therapeutics.
PG  - 154
LID - 10.3389/fonc.2017.00154 [doi]
LID - 154
AB  - Cancer cells share several properties, high proliferation potential, reprogramed 
      metabolism, and resistance to apoptotic cues. Acquiring these hallmarks involves 
      changes in key oncogenes and non-oncogenes essential for cancer cell survival and 
      prosperity, and is accompanied by the increased energy requirements of 
      proliferating cells. Mitochondria occupy a central position in cell life and 
      death with mitochondrial bioenergetics, biosynthesis, and signaling are critical 
      for tumorigenesis. Voltage-dependent anion channel 1 (VDAC1) is situated in the 
      outer mitochondrial membrane (OMM) and serving as a mitochondrial gatekeeper. 
      VDAC1 allowing the transfer of metabolites, fatty acid ions, Ca(2+), reactive 
      oxygen species, and cholesterol across the OMM and is a key player in 
      mitochondrial-mediate apoptosis. Moreover, VDAC1 serves as a hub protein, 
      interacting with diverse sets of proteins from the cytosol, endoplasmic 
      reticulum, and mitochondria that together regulate metabolic and signaling 
      pathways. The observation that VDAC1 is over-expressed in many cancers suggests 
      that the protein may play a pivotal role in cancer cell survival. However, VDAC1 
      is also important in mitochondria-mediated apoptosis, mediating release of 
      apoptotic proteins and interacting with anti-apoptotic proteins, such as B-cell 
      lymphoma 2 (Bcl-2), Bcl-xL, and hexokinase (HK), which are also highly expressed 
      in many cancers. Strategically located in a "bottleneck" position, controlling 
      metabolic homeostasis and apoptosis, VDAC1 thus represents an emerging target for 
      anti-cancer drugs. This review presents an overview on the multi-functional 
      mitochondrial protein VDAC1 performing several functions and interacting with 
      distinct sets of partners to regulate both cell life and death, and highlights 
      the importance of the protein for cancer cell survival. We address recent results 
      related to the mechanisms of VDAC1-mediated apoptosis and the potential of 
      associated proteins to modulate of VDAC1 activity, with the aim of developing 
      VDAC1-based approaches. The first strategy involves modification of cell 
      metabolism using VDAC1-specific small interfering RNA leading to inhibition of 
      cancer cell and tumor growth and reversed oncogenic properties. The second 
      strategy involves activation of cancer cell death using VDAC1-based peptides that 
      prevent cell death induction by anti-apoptotic proteins. Finally, we discuss the 
      potential therapeutic benefits of treatments and drugs leading to enhanced VDAC1 
      expression or targeting VDAC1 to induce apoptosis.
FAU - Shoshan-Barmatz, Varda
AU  - Shoshan-Barmatz V
AD  - Department of Life Sciences, National Institute for Biotechnology in the Negev, 
      Ben-Gurion University of the Negev, Beer-Sheva, Israel.
FAU - Krelin, Yakov
AU  - Krelin Y
AD  - Department of Life Sciences, National Institute for Biotechnology in the Negev, 
      Ben-Gurion University of the Negev, Beer-Sheva, Israel.
FAU - Shteinfer-Kuzmine, Anna
AU  - Shteinfer-Kuzmine A
AD  - Department of Life Sciences, National Institute for Biotechnology in the Negev, 
      Ben-Gurion University of the Negev, Beer-Sheva, Israel.
FAU - Arif, Tasleem
AU  - Arif T
AD  - Department of Life Sciences, National Institute for Biotechnology in the Negev, 
      Ben-Gurion University of the Negev, Beer-Sheva, Israel.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20170731
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC5534932
OTO - NOTNLM
OT  - apoptosis
OT  - cancer
OT  - metabolism
OT  - mitochondria
OT  - voltage-dependent anion channel 1
EDAT- 2017/08/22 06:00
MHDA- 2017/08/22 06:01
PMCR- 2017/01/01
CRDT- 2017/08/22 06:00
PHST- 2016/10/16 00:00 [received]
PHST- 2017/06/28 00:00 [accepted]
PHST- 2017/08/22 06:00 [entrez]
PHST- 2017/08/22 06:00 [pubmed]
PHST- 2017/08/22 06:01 [medline]
PHST- 2017/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2017.00154 [doi]
PST - epublish
SO  - Front Oncol. 2017 Jul 31;7:154. doi: 10.3389/fonc.2017.00154. eCollection 2017.