mTOR pathway in papillary thyroid carcinoma: Different contributions of mTORC1 and mTORC2 complexes for tumor behavior and SLC5A5 mRNA expression

Detalhes bibliográficos
Autor(a) principal: Tavares, C
Data de Publicação: 2018
Outros Autores: Eloy, C, Melo, M, Rocha, AG, Pestana, A, Batista, R, Ferreira, LB, Rios, E, Sobrinho-Simões, M, Soares, P
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: https://hdl.handle.net/10216/127034
Resumo: 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 mTOR pathway in papillary thyroid carcinoma: Different contributions of mTORC1 and mTORC2 complexes for tumor behavior and SLC5A5 mRNA expressionThe 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.MDPI20182018-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10216/127034eng1661-659610.3390/ijms19051448Tavares, CEloy, CMelo, MRocha, AGPestana, ABatista, RFerreira, LBRios, ESobrinho-Simões, MSoares, Pinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-29T16:13:01Zoai:repositorio-aberto.up.pt:10216/127034Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T00:39:12.638347Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv 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
spellingShingle mTOR pathway in papillary thyroid carcinoma: Different contributions of mTORC1 and mTORC2 complexes for tumor behavior and SLC5A5 mRNA expression
Tavares, C
title_short 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_sort mTOR pathway in papillary thyroid carcinoma: Different contributions of mTORC1 and mTORC2 complexes for tumor behavior and SLC5A5 mRNA expression
author Tavares, C
author_facet Tavares, C
Eloy, C
Melo, M
Rocha, AG
Pestana, A
Batista, R
Ferreira, LB
Rios, E
Sobrinho-Simões, M
Soares, P
author_role author
author2 Eloy, C
Melo, M
Rocha, AG
Pestana, A
Batista, R
Ferreira, LB
Rios, E
Sobrinho-Simões, M
Soares, P
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Tavares, C
Eloy, C
Melo, M
Rocha, AG
Pestana, A
Batista, R
Ferreira, LB
Rios, E
Sobrinho-Simões, M
Soares, P
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.
publishDate 2018
dc.date.none.fl_str_mv 2018
2018-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
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dc.identifier.uri.fl_str_mv https://hdl.handle.net/10216/127034
url https://hdl.handle.net/10216/127034
dc.language.iso.fl_str_mv eng
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dc.relation.none.fl_str_mv 1661-6596
10.3390/ijms19051448
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