title: Mitochondrial dynamics protein Drp1 is overexpressed in oncocytic thyroid tumors and regulates cancer cell migration.
abstract: Oncocytic cell tumors are characterized by the accumulation of morphologically abnormal mitochondria in their cells, suggesting a role for abnormal mitochondrial biogenesis in oncocytic cell transformation. Little is known about the reason for the dysmorphology of accumulated mitochondria. The proteins regulating the morphology of mitochondria, the "mitochondria-shaping" proteins, can modulate their size and number; however, nothing is known hitherto about a possible involvement of mitochondrial dynamics in oncocytic cell transformation in tumors. Our aim was to assess the status of the mitochondria morphology and its role in oncocytic cell transformation. We therefore evaluated the expression pattern of the main mitochondrial fusion and fission proteins in a series of thyroid cell tumor samples, as well as in thyroid tumor cell lines, with and without oncocytic cell features. The expression of mitochondrial fusion (Opa1, Mfn1 and Mfn2) and fission (Drp1 and Fis1) proteins were evaluated by immunohistochemistry (IHC) in a series of 88 human thyroid tumors. In vitro studies, for comparative purposes and to deepen the study, were performed using TPC1--a papillary thyroid carcinoma derived cell line--and XTC.UC1, an oncocytic follicular thyroid carcinoma-derived cell line. Both IHC and in vitro protein analyses showed an overall increase in the levels of "mitochondrial-shaping" proteins in oncocytic thyroid tumors. Furthermore, overexpression of the pro-fission protein Drp1 was found to be associated with malignant oncocytic thyroid tumors. Interestingly, genetic and pharmacological blockage of Drp1 activity was able to influence thyroid cancer cells' migration/invasion ability, a feature of tumor malignancy. In this study we show that unbalanced mitochondrial dynamics characterize the malignant features of thyroid oncocytic cell tumors, and participate in the acquisition of the migrating phenotype.
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal; Department of Pathology, Medical Faculty of University of Porto, Porto, Portugal.
authors.forename: André
authors.initials: A
authors.lastname: Ferreira-da-Silva
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Valacca
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal; Department of Pathology, Medical Faculty of University of Porto, Porto, Portugal; Department of Pathology, Hospital S. João, Porto, Portugal.
authors.forename: Elisabete
authors.initials: E
authors.lastname: Rios
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal.
authors.forename: Helena
authors.initials: H
authors.lastname: Pópulo
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal; Department of Pathology, Medical Faculty of University of Porto, Porto, Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Soares
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal; Department of Pathology, Medical Faculty of University of Porto, Porto, Portugal; Department of Pathology, Hospital S. João, Porto, Portugal.
authors.forename: Manuel
authors.initials: M
authors.lastname: Sobrinho-Simões
authors.affiliation: Department of Biology, University of Padua, Padua, Italy; Dulbecco Telethon Institute, Venetian Institute of Molecular Medicine, Padua, Italy; IRCCS Fondazione Santa Lucia, Rome, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Scorrano
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal; Department of Pathology, Medical Faculty of University of Porto, Porto, Portugal.
authors.forename: Valdemar
authors.initials: V
authors.lastname: Máximo
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Rome, Italy; IRCCS Fondazione Santa Lucia, Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Campello
mesh_terms: D018249:Adenoma, Oxyphilic / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D034281:Dynamins; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology*; D063154:Mitochondrial Dynamics; D024101:Mitochondrial Proteins / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000378:metabolism / Q000473:pathology*; D046888:Tissue Array Analysis
chemical_list: C476525:FIS1 protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D020558:GTP Phosphohydrolases; C110768:DNM1L protein, human; D034281:Dynamins
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