Targeting the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway: An emerging treatment strategy for squamous cell lung carcinoma

2014 ◽  
Vol 40 (8) ◽  
pp. 980-989 ◽  
Author(s):  
Joseph Thaddeus Beck ◽  
Amen Ismail ◽  
Christina Tolomeo
Keyword(s):  
Squamous Cell ◽  
Lung Carcinoma ◽  
Treatment Strategy ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Pathway ◽  
Target Of Rapamycin ◽  
Squamous Cell Lung Carcinoma ◽  
Phosphatidylinositol 3 Kinase ◽  
Cell Lung Carcinoma ◽  
Phosphatidylinositol 3

scholarly journals Prolactin activates mammalian target-of-rapamycin through phosphatidylinositol 3-kinase and stimulates phosphorylation of p70S6K and 4E-binding protein-1 in lymphoma cells

2006 ◽  
Vol 190 (2) ◽  
pp. 307-312 ◽  
Author(s):  
Jessica D Bishop ◽  
Wei Lun Nien ◽  
Shauna M Dauphinee ◽  
Catherine K L Too
Keyword(s):  
Binding Protein ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Pathway ◽  
Target Of Rapamycin ◽  
Dependent Manner ◽  
Phosphatidylinositol 3 Kinase ◽  
Lymphoma Cells ◽  
Nb2 Cells ◽  
Initiation Of Translation ◽  
Phosphatidylinositol 3

Mitogens activate the mammalian target-of-rapamycin (mTOR) pathway through phosphatidylinositol 3-kinase (PI3K). The activated mTOR kinase phosphorylates/ activates ribosomal protein S6 kinase (p70S6K) and phosphorylates/inactivates eukaryotic initiation factor 4E-binding protein-1 (4E-BP1), resulting in the initiation of translation and cell-cycle progression. The prolactin receptor signaling cascade has been implicated in crosstalk with the mTOR pathway, but whether prolactin (PRL) directly activates mTOR is not known. This study showed that PRL stimulated the phosphorylation of mTOR, p70S6K, Akt, and Jak2 kinases in a dose- and time-dependent manner in PRL-dependent rat Nb2 lymphoma cells. PRL-stimulated phosphorylation of mTOR was detected as early as 10 min, closely following the phosphorylation of Akt (upstream of mTOR), but preceding that of the downstream p70S6K. PRL activation of mTOR was inhibited by rapamycin (mTOR inhibitor), LY249002, and wortmannin (P13K inhibitors), but not by AG490 (Jak2 inhibitor), indicating that it was mediated by the P13K/Akt, but not Jak2, pathway. PRL also stimulated phosphorylation of 4E-BP1 in Nb2 cells. PRL-induced phosphorylation of p70S6K and 4E-BP1 was inhibited by rapamycin, but not by okadaic acid (inhibitor of protein phosphatase, PP2A). PRL induced a transient interaction between p70S6K and the catalytic subunit of PP2A (PP2Ac) in 1 and 2 h, whereas a PP2Ac–4E-BP1 complex was constitutively present in quiescent and PRL-treated Nb2 cells. These results suggested that p70S6K and 4E-BP1 were substrates of PP2A and the inhibition of mTOR promoted their dephosphorylation by PP2A. In summary, PRL-stimulated phosphorylation of mTOR is mediated by PI3K. PRL-activated mTOR may phosphorylate p70S6K and 4E-BP1 by restraining PP2A.

scholarly journals Forkhead Box Protein O1 Negatively Regulates Skeletal Myocyte Differentiation through Degradation of Mammalian Target of Rapamycin Pathway Components

Endocrinology ◽  
2007 ◽  
Vol 149 (3) ◽  
pp. 1407-1414 ◽  
Author(s):  
Ai-Luen Wu ◽  
Jeong-Ho Kim ◽  
Chongben Zhang ◽  
Terry G. Unterman ◽  
Jie Chen
Keyword(s):  
Myogenic Differentiation ◽  
Mammalian Target Of Rapamycin ◽  
Akt Signaling ◽  
Nutrient Sensing ◽  
Mtor Pathway ◽  
Target Of Rapamycin ◽  
Phosphatidylinositol 3 Kinase ◽  
Forkhead Box ◽  
Myocyte Differentiation ◽  
Phosphatidylinositol 3

The forkhead transcription factor forkhead box protein O1 (FoxO1), a downstream target of phosphatidylinositol 3-kinase/Akt signaling, has been reported to suppress skeletal myocyte differentiation, but the mechanism by which FoxO1 regulates myogenesis is not fully understood. We have previously demonstrated that a nutrient-sensing mammalian target of rapamycin (mTOR) pathway controls the autocrine production of IGF-II and the subsequent phosphatidylinositol 3-kinase/Akt signaling downstream of IGF-II in myogenesis. Here we report a regulatory loop connecting FoxO1 to the mTOR pathway. Inducible activation of a FoxO1 active mutant in the C2C12 mouse myoblasts blocks myogenic differentiation at an early stage and meanwhile leads to proteasome-dependent degradation of a specific subset of components in the mTOR signaling network, including mTOR, raptor, tuberous sclerosis complex 2, and S6 protein kinase 1. This function of FoxO1 requires new protein synthesis, consistent with the idea that a transcriptional target of FoxO1 may be responsible for the degradation of mTOR. We further show that active FoxO1 inhibits IGF-II expression at the transcriptional activation level, through the modulation of mTOR protein levels. Moreover, the addition of exogenous IGF-II fully rescues myocyte differentiation from FoxO inhibition. Taken together, we propose that the mTOR-IGF-II pathway is a major mediator of FoxO’s inhibitory function in skeletal myogenesis.

scholarly journals P1.05-027 Novel Prognostic Gene Expression Signatures for Squamous Cell Lung Carcinoma: A Study by the SPECS Lung Consortium

2017 ◽  
Vol 12 (1) ◽  
pp. S629-S630
Author(s):  
Raphael Bueno ◽  
William Richards ◽  
David Beer ◽  
Karla Ballman ◽  
Ming Tsao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Squamous Cell ◽  
Lung Carcinoma ◽  
Squamous Cell Lung Carcinoma ◽  
Cell Lung Carcinoma ◽  
Prognostic Gene ◽  
Gene Expression Signatures

scholarly journals Leptin Induces Macrophage Lipid Body Formation by a Phosphatidylinositol 3-Kinase- and Mammalian Target of Rapamycin-dependent Mechanism

2007 ◽  
Vol 283 (4) ◽  
pp. 2203-2210 ◽  
Author(s):  
Clarissa M. Maya-Monteiro ◽  
Patricia E. Almeida ◽  
Heloisa D'Ávila ◽  
Aline S. Martins ◽  
Ana Paula Rezende ◽  
...  
Keyword(s):  
Mammalian Target Of Rapamycin ◽  
Lipid Body ◽  
Target Of Rapamycin ◽  
Phosphatidylinositol 3 Kinase ◽  
Body Formation ◽  
Dependent Mechanism ◽  
Phosphatidylinositol 3
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