PVALB diminishes [Ca2+] and alters mitochondrial features in follicular thyroid carcinoma cells through AKT/GSK3 beta pathway

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dc.contributor.author Mendes, Thais Biude [UNIFESP]
dc.contributor.author Nozima, Bruno Heidi [UNIFESP]
dc.contributor.author Budu, Alexandre [UNIFESP]
dc.contributor.author de Souza, Rodrigo Barbosa [UNIFESP]
dc.contributor.author Braga Catroxo, Marcia Helena
dc.contributor.author Delcelo, Rosana [UNIFESP]
dc.contributor.author Gazarini, Marcos Leoni [UNIFESP]
dc.contributor.author Cerutti, Janete Maria [UNIFESP]
dc.date.accessioned 2019-07-22T15:46:47Z
dc.date.available 2019-07-22T15:46:47Z
dc.date.issued 2016
dc.identifier http://dx.doi.org/10.1530/ERC-16-0181
dc.identifier.citation Endocrine-Related Cancer. Bristol, v. 23, n. 9, p. 769-782, 2016.
dc.identifier.issn 1351-0088
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/51083
dc.description.abstract We have identified previously a panel of markers (C1orf24, ITM1 and PVALB) that can help to discriminate benign from malignant thyroid lesions. C1orf24 and ITM1 are specifically helpful for detecting a wide range of thyroid carcinomas, and PVALB is particularly valuable for detecting the benign Hurthle cell adenoma . Although these markers may ultimately help patient care, the current understanding of their biological functions remains largely unknown. In this article, we investigated whether PVALB is critical for the acquisition of Hurthle cell features and explored the molecular mechanism underlying the phenotypic changes. Through ectopic expression of PVALB in thyroid carcinoma cell lines (FTC-133 and WRO), we demonstrated that PVALB sequesters free cytoplasmic Ca-2+,Ca- which ultimately lowers calcium levels and precludes endoplasmic reticulum (ER) Ca2+ refilling. These results were accompanied by induced expression of PERK, an ER stress marker. Additionally, forced expression of PVALB reduces Ca2+ inflow in the mitochondria, which can in turn cause changes in mitochondria morphology, increase mitochondria number and alter subcellular localization. These findings share striking similarity to those observed in Hurthle cell tumors. Moreover, PVALB inhibits cell growth and induces cell death, most likely through the AKT/GSK-3 beta. Finally, PVALB expression coincides with Ca2+ deposits in HCA tissues. Our data support the hypothesis that the loss of PVALB plays a role in the pathogenesis of thyroid tumors. en
dc.description.sponsorship Sao Paulo State Research Foundation - FAPESP [2013/03867-5, 2014/06570-6, 2009/54598-9]
dc.description.sponsorship Brazilian Research Council (CNPq)
dc.description.sponsorship FAPESP
dc.description.sponsorship CNPq
dc.format.extent 769-782
dc.language.iso eng
dc.publisher Bioscientifica Ltd
dc.rights Acesso restrito
dc.subject PVALB en
dc.subject Hurthle cell adenoma en
dc.subject thyroid cancer en
dc.subject AKT and GSK beta en
dc.title PVALB diminishes [Ca2+] and alters mitochondrial features in follicular thyroid carcinoma cells through AKT/GSK3 beta pathway en
dc.type Artigo
dc.description.affiliation Univ Fed Sao Paulo, Dept Morphol & Genet, Div Genet, Genet Bases Thyroid Tumors Lab, Sao Paulo, Brazil
dc.description.affiliation Univ Fed Sao Paulo, Dept Biophys, Enzymol Lab, Sao Paulo, Brazil
dc.description.affiliation Inst Biol, Ctr Res & Dev Anim Hlth, Lab Electron Microscopy, Sao Paulo, Brazil
dc.description.affiliation Univ Fed Sao Paulo, Dept Pathol, Sao Paulo, Brazil
dc.description.affiliation Univ Fed Sao Paulo, Dept Biosci, Cell Signaling Lab Plasmodium, Santos, SP, Brazil
dc.description.affiliationUnifesp Univ Fed Sao Paulo, Dept Morphol & Genet, Div Genet, Genet Bases Thyroid Tumors Lab, Sao Paulo, Brazil
dc.description.affiliationUnifesp Univ Fed Sao Paulo, Dept Biophys, Enzymol Lab, Sao Paulo, Brazil
dc.description.affiliationUnifesp Univ Fed Sao Paulo, Dept Pathol, Sao Paulo, Brazil
dc.description.affiliationUnifesp Univ Fed Sao Paulo, Dept Biosci, Cell Signaling Lab Plasmodium, Santos, SP, Brazil
dc.description.sponsorshipID FAPESP:2013/03867-5
dc.description.sponsorshipID 2014/06570-6
dc.description.sponsorshipID 2009/54598-9
dc.identifier.doi 10.1530/ERC-16-0181
dc.description.source Web of Science
dc.identifier.wos WOS:000384190100014



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