title: Hypoxic VDAC1: a potential mitochondrial marker for cancer therapy.
abstract: Finding new therapeutic targets to fight cancer is an ongoing quest. Because of insufficiencies in tumor vasculature, cells often are exposed to a hostile microenvironment that is low in oxygen (hypoxic) and nutrients. Thus, tumor cells face the challenge of finding new sources of energy and defying apoptosis, which allow them to survive, grow, and colonize other tissues. Eradicating specifically these hypoxic cells is one of the many goals of anticancer therapies. The mitochondrial voltage-dependent anion channel (VDAC) is a protein at the crossroads of metabolic and survival pathways. As its name suggests, VDAC is involved in ion transport as well as adenosine triphosphate and NAD(+) transport. We recently reported the presence in tumor cells of a novel hypoxia-induced form of VDAC. This form, a C-terminal truncated protein (VDAC1-ΔC), was associated in some cancer cell lines with a high output of adenosine triphosphate and a strong resistance to chemotherapy-induced apoptosis. Furthermore, VDAC1-ΔC was detected in tissues of 50 % of 46 patients with lung cancer. This review examines the significance of this new form of VDAC1 for anticancer therapy.
authors.affiliation: Institute for Research on Cancer and Aging, Nice (IRCAN), CNRS UMR7284, INSERM U1081, University of Nice, Nice, France.
authors.forename: M Christiane
authors.initials: MC
authors.lastname: Brahimi-Horn
authors.forename: N M
authors.initials: NM
authors.lastname: Mazure
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015687:Cell Hypoxia / Q000235:genetics; D006801:Humans; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D020033:Protein Isoforms / Q000502:physiology; D050995:Voltage-Dependent Anion Channel 1 / Q000502:physiology*
chemical_list: D014408:Biomarkers, Tumor; D020033:Protein Isoforms; C494762:VDAC1 protein, human; D050995:Voltage-Dependent Anion Channel 1