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

Autor(es)

Mendes, Thais Biude ; Nozima, Bruno Heidi ; Budu, Alexandre ; de Souza, Rodrigo Barbosa ; Braga Catroxo, Marcia Helena ; Delcelo, Rosana ; Gazarini, Marcos Leoni ; Cerutti, Janete Maria

• Tipo de documento: Artigo Científico
• Fonte: Endocrine-Related Cancer; v. 23, n. 9, p. 769-782, SEP 2016.
• Citações Web of Science: 1

Resumo

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. (AU)

• Processo FAPESP: 09/54598-9 - Proteólise intracelular em parasitas da malária: caracterização e inibição de proteases em um novo ensaio para o ‘screening’ de drogas antimaláricas
• Beneficiário: Marcos Leoni Gazarini Dutra
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
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• Modalidade de apoio: Auxílio à Pesquisa - Temático
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• Modalidade de apoio: Auxílio à Pesquisa - Regular