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mTOR Pathway in Papillary Thyroid Carcinoma: Different Contributions of mTORC1 and mTORC2 Complexes for Tumor Behavior and SLC5A5 mRNA Expression

The mammalian target of rapamycin (mTOR) pathway is overactivated in thyroid cancer (TC). We previously demonstrated that phospho-mTOR expression is associated with tumor aggressiveness, therapy resistance, and lower mRNA expression of SLC5A5 in papillary thyroid carcinoma (PTC), while phospho-S6 (m...

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Autores principales: Tavares, Catarina, Eloy, Catarina, Melo, Miguel, Gaspar da Rocha, Adriana, Pestana, Ana, Batista, Rui, Bueno Ferreira, Luciana, Rios, Elisabete, Sobrinho Simões, Manuel, Soares, Paula
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983778/
https://www.ncbi.nlm.nih.gov/pubmed/29757257
http://dx.doi.org/10.3390/ijms19051448
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author Tavares, Catarina
Eloy, Catarina
Melo, Miguel
Gaspar da Rocha, Adriana
Pestana, Ana
Batista, Rui
Bueno Ferreira, Luciana
Rios, Elisabete
Sobrinho Simões, Manuel
Soares, Paula
author_facet Tavares, Catarina
Eloy, Catarina
Melo, Miguel
Gaspar da Rocha, Adriana
Pestana, Ana
Batista, Rui
Bueno Ferreira, Luciana
Rios, Elisabete
Sobrinho Simões, Manuel
Soares, Paula
author_sort Tavares, Catarina
collection PubMed
description The mammalian target of rapamycin (mTOR) pathway is overactivated in thyroid cancer (TC). We previously demonstrated that phospho-mTOR expression is associated with tumor aggressiveness, therapy resistance, and lower mRNA expression of SLC5A5 in papillary thyroid carcinoma (PTC), while phospho-S6 (mTORC1 effector) expression was associated with less aggressive clinicopathological features. The distinct behavior of the two markers led us to hypothesize that mTOR activation may be contributing to a preferential activation of the mTORC2 complex. To approach this question, we performed immunohistochemistry for phospho-AKT Ser473 (mTORC2 effector) in a series of 182 PTCs previously characterized for phospho-mTOR and phospho-S6 expression. We evaluated the impact of each mTOR complex on SLC5A5 mRNA expression by treating cell lines with RAD001 (mTORC1 blocker) and Torin2 (mTORC1 and mTORC2 blocker). Phospho-AKT Ser473 expression was positively correlated with phospho-mTOR expression. Nuclear expression of phospho-AKT Ser473 was significantly associated with the presence of distant metastases. Treatment of cell lines with RAD001 did not increase SLC5A5 mRNA levels, whereas Torin2 caused a ~6 fold increase in SLC5A5 mRNA expression in the TPC1 cell line. In PTC, phospho-mTOR activation may lead to the activation of the mTORC2 complex. Its downstream effector, phospho-AKT Ser473, may be implicated in distant metastization, therapy resistance, and downregulation of SLC5A5 mRNA expression.
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spelling pubmed-59837782018-06-05 mTOR Pathway in Papillary Thyroid Carcinoma: Different Contributions of mTORC1 and mTORC2 Complexes for Tumor Behavior and SLC5A5 mRNA Expression Tavares, Catarina Eloy, Catarina Melo, Miguel Gaspar da Rocha, Adriana Pestana, Ana Batista, Rui Bueno Ferreira, Luciana Rios, Elisabete Sobrinho Simões, Manuel Soares, Paula Int J Mol Sci Article The mammalian target of rapamycin (mTOR) pathway is overactivated in thyroid cancer (TC). We previously demonstrated that phospho-mTOR expression is associated with tumor aggressiveness, therapy resistance, and lower mRNA expression of SLC5A5 in papillary thyroid carcinoma (PTC), while phospho-S6 (mTORC1 effector) expression was associated with less aggressive clinicopathological features. The distinct behavior of the two markers led us to hypothesize that mTOR activation may be contributing to a preferential activation of the mTORC2 complex. To approach this question, we performed immunohistochemistry for phospho-AKT Ser473 (mTORC2 effector) in a series of 182 PTCs previously characterized for phospho-mTOR and phospho-S6 expression. We evaluated the impact of each mTOR complex on SLC5A5 mRNA expression by treating cell lines with RAD001 (mTORC1 blocker) and Torin2 (mTORC1 and mTORC2 blocker). Phospho-AKT Ser473 expression was positively correlated with phospho-mTOR expression. Nuclear expression of phospho-AKT Ser473 was significantly associated with the presence of distant metastases. Treatment of cell lines with RAD001 did not increase SLC5A5 mRNA levels, whereas Torin2 caused a ~6 fold increase in SLC5A5 mRNA expression in the TPC1 cell line. In PTC, phospho-mTOR activation may lead to the activation of the mTORC2 complex. Its downstream effector, phospho-AKT Ser473, may be implicated in distant metastization, therapy resistance, and downregulation of SLC5A5 mRNA expression. MDPI 2018-05-13 /pmc/articles/PMC5983778/ /pubmed/29757257 http://dx.doi.org/10.3390/ijms19051448 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tavares, Catarina
Eloy, Catarina
Melo, Miguel
Gaspar da Rocha, Adriana
Pestana, Ana
Batista, Rui
Bueno Ferreira, Luciana
Rios, Elisabete
Sobrinho Simões, Manuel
Soares, Paula
mTOR Pathway in Papillary Thyroid Carcinoma: Different Contributions of mTORC1 and mTORC2 Complexes for Tumor Behavior and SLC5A5 mRNA Expression
title mTOR Pathway in Papillary Thyroid Carcinoma: Different Contributions of mTORC1 and mTORC2 Complexes for Tumor Behavior and SLC5A5 mRNA Expression
title_full mTOR Pathway in Papillary Thyroid Carcinoma: Different Contributions of mTORC1 and mTORC2 Complexes for Tumor Behavior and SLC5A5 mRNA Expression
title_fullStr mTOR Pathway in Papillary Thyroid Carcinoma: Different Contributions of mTORC1 and mTORC2 Complexes for Tumor Behavior and SLC5A5 mRNA Expression
title_full_unstemmed mTOR Pathway in Papillary Thyroid Carcinoma: Different Contributions of mTORC1 and mTORC2 Complexes for Tumor Behavior and SLC5A5 mRNA Expression
title_short mTOR Pathway in Papillary Thyroid Carcinoma: Different Contributions of mTORC1 and mTORC2 Complexes for Tumor Behavior and SLC5A5 mRNA Expression
title_sort mtor pathway in papillary thyroid carcinoma: different contributions of mtorc1 and mtorc2 complexes for tumor behavior and slc5a5 mrna expression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983778/
https://www.ncbi.nlm.nih.gov/pubmed/29757257
http://dx.doi.org/10.3390/ijms19051448
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