mTOR Pathway in Papillary Thyroid Carcinoma: Different Contributions of mTORC1 and mTORC2 Complexes for Tumor Behavior and SLC5A5 mRNA Expression
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , , , , |
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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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 |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
MDPI |
publisher.none.fl_str_mv |
MDPI |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799134125883392000 |