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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Mendes, Thais Biude ; Nozima, Bruno Heidi ; Budu, Alexandre ; de Souza, Rodrigo Barbosa ; Braga Catroxo, Marcia Helena ; Delcelo, Rosana ; Gazarini, Marcos Leoni ; Cerutti, Janete Maria
Total Authors: 8
Document type: Journal article
Source: Endocrine-Related Cancer; v. 23, n. 9, p. 769-782, SEP 2016.
Web of Science Citations: 1
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. (AU)

FAPESP's process: 13/03867-5 - Analysis of copy number variation (CNV) in pacientes of a family with men 2A and P.G533C mutation in the RET gene: identification of CNV regions associated with genesis and progression of medullary thyroid carcinoma
Grantee:Janete Maria Cerutti
Support type: Regular Research Grants
FAPESP's process: 14/06570-6 - Comprehensive whole exome, paired-end RNA and genome sequencing: new insights into genetic bases of thyroid carcinoma in pediatric and adult ages and applications in clinical practice
Grantee:Janete Maria Cerutti
Support type: Research Projects - Thematic Grants