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

摘要: The mammalian target of rapamycin (mTOR) pathway is overactivated in thyroid cancer (TC). We previously demonstrated that phospho-mTOR expression associated with tumor aggressiveness, therapy resistance, and lower mRNA SLC5A5 papillary carcinoma (PTC), while phospho-S6 (mTORC1 effector) was less aggressive clinicopathological features. distinct behavior the two markers led us to hypothesize mTOR activation may be contributing a preferential mTORC2 complex. To approach this question, we performed immunohistochemistry for phospho-AKT Ser473 (mTORC2 series 182 PTCs characterized expression. evaluated impact each complex on by treating cell lines RAD001 blocker) Torin2 blocker). Phospho-AKT positively correlated Nuclear significantly presence distant metastases. Treatment did not increase levels, whereas caused ~6 fold TPC1 line. In PTC, lead Its downstream effector, Ser473, implicated metastization, downregulation