title: The proteomic 2D-DIGE approach reveals the protein voltage-dependent anion channel 2 as a potential therapeutic target in epithelial thyroid tumours.
abstract: We investigated the role of VDAC2 in human epithelial thyroid tumours using proteomic 2D-DIGE analysis and qRT-PCR. We found a significant up-regulation of VDAC2 in thyroid tumours and in thyroid tumour cell lines (TPC-1 and CAL-62). We did not detect overexpression of VDAC2 in a normal thyroid cell line (Nthy-ori 3-1). Silico analysis revealed that two proteins, BAK1 and BAX, had a strong relationship with VDAC2. BAK1 gene expression showed down-regulation in thyroid tumours (follicular and papillary tumours) and in TPC-1 and CAL-62 cell lines. Transient knockdown of VDAC2 in TPC-1 and CAL-62 promoted upregulation of the BAK1 gene and protein expression, and increased susceptibility to sorafenib treatment. Overexpression of the BAK1 gene in CAL-62 showed lower sorafenib sensitivity than VDAC2 knockdown cells. We propose the VDAC2 gene as a novel therapeutic target in these tumours.
authors.affiliation: Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Institut d'Investigació Biomèdica Sant Pau (IIB), Autonomous University, Barcelona, Spain; EDUAB-HSP Neoplasia Thyroid Study Group, IIB, Autonomous University, Barcelona, Spain. Electronic address: emato@santpau.cat.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Mato
authors.affiliation: Proteomics Unit, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.
authors.forename: Sílvia
authors.initials: S
authors.lastname: Barceló-Batllori
authors.affiliation: Centro Investigaciones Biomédicas Aragón (CIBA), Instituto Aragonés de Ciencias de la Salud-Instituto de Investigación Sanitaria Aragón (IACS-IIS), Zaragoza, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Orera
authors.affiliation: EDUAB-HSP Neoplasia Thyroid Study Group, IIB, Autonomous University, Barcelona, Spain.
authors.forename: Laia
authors.initials: L
authors.lastname: Selva
authors.affiliation: EDUAB-HSP Neoplasia Thyroid Study Group, IIB, Autonomous University, Barcelona, Spain.
authors.forename: Martina
authors.initials: M
authors.lastname: Corra
authors.affiliation: EDUAB-HSP Neoplasia Thyroid Study Group, IIB, Autonomous University, Barcelona, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Institut d'Investigació Biomèdica Sant Pau (IIB), Autonomous University, Barcelona, Spain.
authors.forename: Cintia
authors.initials: C
authors.lastname: González
authors.affiliation: Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Institut d'Investigació Biomèdica Sant Pau (IIB), Autonomous University, Barcelona, Spain; EDUAB-HSP Neoplasia Thyroid Study Group, IIB, Autonomous University, Barcelona, Spain.
authors.forename: Olga
authors.initials: O
authors.lastname: Bell
authors.affiliation: Department of Pathology, Hospital de la Santa Creu i Sant Pau, Autonomous University, Barcelona, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Lerma
authors.affiliation: General Surgery, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Moral
authors.affiliation: General Surgery, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain.
authors.forename: José Ignacio
authors.initials: JI
authors.lastname: Pérez
authors.affiliation: Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Institut d'Investigació Biomèdica Sant Pau (IIB), Autonomous University, Barcelona, Spain; EDUAB-HSP Neoplasia Thyroid Study Group, IIB, Autonomous University, Barcelona, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: de Leiva
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000494:pharmacology; D040901:Proteomics / Q000379:methods*; D000077157:Sorafenib; D013964:Thyroid Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D057825:Two-Dimensional Difference Gel Electrophoresis / Q000379:methods*; D015854:Up-Regulation; D050996:Voltage-Dependent Anion Channel 2 / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000235:genetics / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494772:BAK1 protein, human; C494826:BAX protein, human; D010671:Phenylurea Compounds; C494765:VDAC2 protein, human; D050996:Voltage-Dependent Anion Channel 2; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D009536:Niacinamide; D000077157:Sorafenib
keywords: Epithelial thyroid tumours; Therapeutic target; Voltage-dependent anion channel 2