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

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

Author Mendes, Thais Biude Autor UNIFESP Google Scholar
Nozima, Bruno Heidi Autor UNIFESP Google Scholar
Budu, Alexandre Autor UNIFESP Google Scholar
de Souza, Rodrigo Barbosa Autor UNIFESP Google Scholar
Braga Catroxo, Marcia Helena Google Scholar
Delcelo, Rosana Autor UNIFESP Google Scholar
Gazarini, Marcos Leoni Autor UNIFESP Google Scholar
Cerutti, Janete Maria Autor UNIFESP Google Scholar
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.
Keywords PVALB
Hurthle cell adenoma
thyroid cancer
AKT and GSK beta
Language English
Sponsor Sao Paulo State Research Foundation - FAPESP [2013/03867-5, 2014/06570-6, 2009/54598-9]
Brazilian Research Council (CNPq)
FAPESP
CNPq
Grant number FAPESP:2013/03867-5
2014/06570-6
2009/54598-9
Date 2016
Published in Endocrine-Related Cancer. Bristol, v. 23, n. 9, p. 769-782, 2016.
ISSN 1351-0088 (Sherpa/Romeo, impact factor)
Publisher Bioscientifica Ltd
Extent 769-782
Origin http://dx.doi.org/10.1530/ERC-16-0181
Access rights Closed access
Type Article
Web of Science ID WOS:000384190100014
URI http://repositorio.unifesp.br/handle/11600/51083

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