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Title: | mTOR Pathway in Papillary Thyroid Carcinoma: Different Contributions of mTORC1 and mTORC2 Complexes for Tumor Behavior and SLC5A5 mRNA Expression | Authors: | Tavares, Catarina Eloy, Catarina Melo, Miguel Gaspar da Rocha, Adriana Pestana, Ana Batista, Rui Bueno Ferreira, Luciana Rios, Elisabete Sobrinho-Simões, Manuel Soares, Paula |
Keywords: | mTOR; thyroid cancer; sodium iodide symporter (NIS)/SLC5A5 | Issue Date: | 13-May-2018 | Publisher: | MDPI | Serial title, monograph or event: | International Journal of Molecular Sciences | Volume: | 19 | Issue: | 5 | Abstract: | 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. | URI: | https://hdl.handle.net/10316/107692 | ISSN: | 1422-0067 | DOI: | 10.3390/ijms19051448 | Rights: | openAccess |
Appears in Collections: | FMUC Medicina - Artigos em Revistas Internacionais |
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mTOR pathway in papillary thyroid carcinoma Different contributions of mTORC1 and mTORC2 complexes for tumor behavior and SLC5A5 mRNA expression.pdf | 3.13 MB | Adobe PDF | View/Open |
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