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EIF4E MTOR (1 - 2 of 2)
PMID: 20177775
Effect of combination treatment of rapamycin and isoflavones on mTOR pathway in human glioblastoma (U87) cells.
... on mTOR pathway and activation of ... and eIF4E in ...   (details)

EIF4E MTOR

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

PMID: 20177775

Effect of combination treatment of rapamycin and isoflavones on mTOR pathway in human glioblastoma (U87) cells.
Source

Neurochemical research (July 2010)

Abstract

Effect of combination treatment of rapamycin and isoflavones on mTOR pathway in human glioblastoma (U87) cells. Glioblastoma Multiforme (GBM) is a malignant primary brain tumor associated with poor survival rate. PI3K/Akt pathway is highly upregulated in gliomas due to deletion or mutation of PTEN and its activation is associated with tumor grade. mTOR is downstream from PI3K/Akt pathway and it initiates translation through its action on S6K and 4E-BP1. mTOR is an important therapeutic target in many cancers, including glioblastomas. Rapamycin and its analogues are known to inhibit mTOR pathway; however, they also show simultaneous upregulation of Akt and eIF4E survival pathways on inhibition of mTOR, rendering cells more resistant to rapamycin treatment. In this study we investigated the effect of combination treatment of rapamycin with isoflavones such as genistein and biochanin A on mTOR pathway and activation of Akt and eIF4E in human glioblastoma (U87) cells. Our results show that combination treatment of rapamycin with isoflavones, especially biochanin A at 50 muM, decreased the phosphorylation of Akt and eIF4E proteins and rendered U87 cells more sensitive to rapamycin treatment when compared to cells treated with rapamycin alone. These results suggest the importance of combining chemopreventive with chemotherapeutic agents in order to increase the efficacy of chemotherapeutic drugs.

PMID: 23722547
Vitronectin-avß3 Integrin Engagement Directs Hypoxia-Resistant mTOR Activity and Sustained Protein Synthesis Linked to Invasion by Breast Cancer Cells.
... of mTOR despite hypoxia involves release ... factor eIF4E from ...   (details)

EIF4E MTOR

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

PMID: 23722547

Vitronectin-avß3 Integrin Engagement Directs Hypoxia-Resistant mTOR Activity and Sustained Protein Synthesis Linked to Invasion by Breast Cancer Cells.
Source

Cancer research (7/15/2013)

Abstract

Vitronectin-avß3 Integrin Engagement Directs Hypoxia-Resistant mTOR Activity and Sustained Protein Synthesis Linked to Invasion by Breast Cancer Cells. The tumor microenvironment is a crucial player in the ability of cancer cells to acquire the ability to survive under the hypoxic environment and promote migration and invasion. Translational regulation is an essential part of cancer development and progression. Protein synthesis consumes considerable cellular metabolic energy and is therefore highly regulated, in turn controlling tumor cell proliferation and survival in extreme tumor-host conditions. Protein synthesis is typically downregulated by hypoxia, impairing cell proliferation and migration. Here, we show that breast cancer cells expressing integrin avß3, when engaging the extracellular matrix (ECM) protein vitronectin, strongly upregulate both mTOR activity and cap-dependent mRNA translation, which overrides their inhibition by hypoxia and facilitates tumor cell invasion. Interaction of vitronectin with integrin avß3 results in the continued activation of the kinase mTOR despite hypoxia through a mechanism that is dependent on integrin-linked kinase but is independent of focal adhesion kinase. Continuous activation of mTOR despite hypoxia involves release of translation initiation factor eIF4E from its repressor protein 4E-BP1, which is required for vitronectin-mediated tumor cell invasion. As integrin avß3 is associated with breast cancer cell invasion and metastasis to bone, we propose that the interaction with specific ECM proteins can influence cancer cell invasion, in part, by hyperactivation of mTOR, thereby promoting and sustaining protein synthesis under hypoxic conditions. Cancer Res; 73 (14); 4571-8. ©2013 AACR.