RESUMO
The mammalian target of rapamycin complex 2 (mTORC2) plays critical roles in various biological processes. To better understand the functions of mTORC2 and the underlying molecular mechanisms, we established a stable cell line with reduced Rictor, a specific component in mTORC2, and investigated the quantitative changes of the cellular proteome. As a result, we observed that 101 proteins were down-regulated and 50 proteins were up-regulated in Rictor knockdown cells. A protein-protein interaction network regulated by Rictor/mTORC2 was established, showing that Rictor/mTORC2 was involved in various cellular processes. Intriguingly, gene ontology analysis indicated that the proteome regulated by Rictor/mTORC2 was significantly involved with cell adhesion. Rictor knockdown affected the expressions of multiple cell adhesion associated molecules, e.g. integrin α-5 (ITGA5), transforming growth factor beta-1-induced transcript 1 protein (TGFB1I1), lysyl oxidase homologue 2 (LOXL2), etc. Further study suggested that Rictor/mTORC2 may regulate cell adhesion and invasion by modulating the expressions of these cell adhesion molecules through AKT. Taken together, this study maps the proteome regulated by Rictor/mTORC2 and reveals its role in promoting renal cancer cell invasion through modulating cell adhesion and migration.
Assuntos
Proteoma/metabolismo , Proteômica/métodos , Proteína Companheira de mTOR Insensível à Rapamicina/metabolismo , Adesão Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Humanos , Invasividade Neoplásica , Mapas de Interação de Proteínas/genética , Proteoma/genética , Interferência de RNA , Proteína Companheira de mTOR Insensível à Rapamicina/genética , Transdução de Sinais/genéticaRESUMO
Immune thrombocytopenia (ITP) is an acquired immune-mediated disorder with regulatory T cells (Tregs) reduction. Recent studies have shown that low-dose interleukin-2 can preferentially induce Treg expansion in vivo, and therefore offers a therapeutic strategy against immune thrombocytopenia. We have demonstrated in a previous study that Tregs and platelet counts significantly improve in an adult with ITP following low-dose IL-2 treatment. Here we report the efficacy of low-dose IL-2 in another three adults with immune thrombocytopenia who failed the first-line treatment. All patients received a dose of 1.0 million IU IL-2/day for 5 consecutive days per week as a cycle for 2 or 4 weeks. In addition to IL-2, vincristine (2 mg IV weekly × 3 weeks) was added to one patient as a combination therapy. No specific treatment was added in the other two patients. Two cases exhibited significantly increased platelet counts with improved levels of Tregs, while no changes were observed for the remaining patient. In summary, administration of daily subcutaneous low-dose IL-2 was safe, and it may be a new therapeutic option for treatment of ITP, especially refractory ITP. © 2017 International Clinical Cytometry Society.