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, Catarina
Data de Publicação: 2018
Outros Autores: Eloy, Catarina, Melo, Miguel, Gaspar da Rocha, Adriana, Pestana, Ana, Batista, Rui, Bueno Ferreira, Luciana, Rios, Elisabete, Sobrinho-Simões, Manuel, Soares, Paula
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10316/107692
https://doi.org/10.3390/ijms19051448
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 ExpressionmTORthyroid cancersodium iodide symporter (NIS)/SLC5A5Carcinoma, PapillaryCell Line, TumorGene Expression Regulation, NeoplasticHumansImmunohistochemistryMechanistic Target of Rapamycin Complex 1Mechanistic Target of Rapamycin Complex 2PhosphorylationProto-Oncogene Proteins B-rafProto-Oncogene Proteins c-aktRNA, MessengerSymportersTOR Serine-Threonine KinasesThyroid Cancer, PapillaryThyroid NeoplasmsSignal TransductionThe 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.MDPI2018-05-13info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/107692http://hdl.handle.net/10316/107692https://doi.org/10.3390/ijms19051448eng1422-0067Tavares, CatarinaEloy, CatarinaMelo, MiguelGaspar da Rocha, AdrianaPestana, AnaBatista, RuiBueno Ferreira, LucianaRios, ElisabeteSobrinho-Simões, ManuelSoares, Paulainfo: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:RCAAP2023-07-27T09:54:28Zoai:estudogeral.uc.pt:10316/107692Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:24:00.846303Repositório 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, Catarina
mTOR
thyroid cancer
sodium iodide symporter (NIS)/SLC5A5
Carcinoma, Papillary
Cell Line, Tumor
Gene Expression Regulation, Neoplastic
Humans
Immunohistochemistry
Mechanistic Target of Rapamycin Complex 1
Mechanistic Target of Rapamycin Complex 2
Phosphorylation
Proto-Oncogene Proteins B-raf
Proto-Oncogene Proteins c-akt
RNA, Messenger
Symporters
TOR Serine-Threonine Kinases
Thyroid Cancer, Papillary
Thyroid Neoplasms
Signal Transduction
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, Catarina
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_role author
author2 Eloy, Catarina
Melo, Miguel
Gaspar da Rocha, Adriana
Pestana, Ana
Batista, Rui
Bueno Ferreira, Luciana
Rios, Elisabete
Sobrinho-Simões, Manuel
Soares, Paula
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Tavares, Catarina
Eloy, Catarina
Melo, Miguel
Gaspar da Rocha, Adriana
Pestana, Ana
Batista, Rui
Bueno Ferreira, Luciana
Rios, Elisabete
Sobrinho-Simões, Manuel
Soares, Paula
dc.subject.por.fl_str_mv mTOR
thyroid cancer
sodium iodide symporter (NIS)/SLC5A5
Carcinoma, Papillary
Cell Line, Tumor
Gene Expression Regulation, Neoplastic
Humans
Immunohistochemistry
Mechanistic Target of Rapamycin Complex 1
Mechanistic Target of Rapamycin Complex 2
Phosphorylation
Proto-Oncogene Proteins B-raf
Proto-Oncogene Proteins c-akt
RNA, Messenger
Symporters
TOR Serine-Threonine Kinases
Thyroid Cancer, Papillary
Thyroid Neoplasms
Signal Transduction
topic mTOR
thyroid cancer
sodium iodide symporter (NIS)/SLC5A5
Carcinoma, Papillary
Cell Line, Tumor
Gene Expression Regulation, Neoplastic
Humans
Immunohistochemistry
Mechanistic Target of Rapamycin Complex 1
Mechanistic Target of Rapamycin Complex 2
Phosphorylation
Proto-Oncogene Proteins B-raf
Proto-Oncogene Proteins c-akt
RNA, Messenger
Symporters
TOR Serine-Threonine Kinases
Thyroid Cancer, Papillary
Thyroid Neoplasms
Signal Transduction
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 2018-05-13
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10316/107692
http://hdl.handle.net/10316/107692
https://doi.org/10.3390/ijms19051448
url http://hdl.handle.net/10316/107692
https://doi.org/10.3390/ijms19051448
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 1422-0067
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
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dc.publisher.none.fl_str_mv MDPI
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repository.mail.fl_str_mv
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