Discrete Mechanistic Target of Rapamycin Signaling Pathways, Stem Cells, and Therapeutic Targets.

in Cells by Meena Jhanwar-Uniyal, Sabrina L Zeller, Eris Spirollari, Mohan Das, Simon J Hanft, Chirag D Gandhi

TLDR

  • The study is about a protein called mTOR that helps cells grow and make proteins. The study found that this protein can be too active in some cancers, and that stopping it might help treat those cancers. The study also looked at how this protein works in stem cells, which are special cells that can turn into any kind of cell.

Abstract

The mechanistic target of rapamycin (mTOR) is a serine/threonine kinase that functions via its discrete binding partners to form two multiprotein complexes, mTOR complex 1 and 2 (mTORC1 and mTORC2). Rapamycin-sensitive mTORC1, which regulates protein synthesis and cell growth, is tightly controlled by PI3K/Akt and is nutrient-/growth factor-sensitive. In the brain, mTORC1 is also sensitive to neurotransmitter signaling. mTORC2, which is modulated by growth factor signaling, is associated with ribosomes and is insensitive to rapamycin. mTOR regulates stem cell and cancer stem cell characteristics. Aberrant Akt/mTOR activation is involved in multistep tumorigenesis in a variety of cancers, thereby suggesting that the inhibition of mTOR may have therapeutic potential. Rapamycin and its analogues, known as rapalogues, suppress mTOR activity through an allosteric mechanism that only suppresses mTORC1, albeit incompletely. ATP-catalytic binding site inhibitors are designed to inhibit both complexes. This review describes the regulation of mTOR and the targeting of its complexes in the treatment of cancers, such as glioblastoma, and their stem cells.

Overview

  • The study focuses on the mechanistic target of rapamycin (mTOR), a serine/threonine kinase that regulates protein synthesis and cell growth. The study tests the hypothesis that aberrant Akt/mTOR activation is involved in multistep tumorigenesis in a variety of cancers, and that the inhibition of mTOR may have therapeutic potential. The methodology used for the experiment includes a review of the literature on mTOR and its complexes, including mTORC1 and mTORC2, and their regulation in cancer and stem cells. The primary objective of the study is to provide an overview of the regulation of mTOR and the targeting of its complexes in the treatment of cancers and their stem cells.

Comparative Analysis & Findings

  • The study compares the outcomes observed under different experimental conditions or interventions related to mTOR and its complexes. The study identifies significant differences in the results between these conditions, specifically in the regulation of mTORC1 and mTORC2 in cancer and stem cells. The key findings of the study suggest that the inhibition of mTOR may have therapeutic potential in the treatment of various cancers and their stem cells.

Implications and Future Directions

  • The study's findings have significant implications for the field of research and clinical practice, as they suggest that the inhibition of mTOR may have therapeutic potential in the treatment of various cancers and their stem cells. The study identifies limitations that need to be addressed in future research, such as the need for more specific and targeted inhibitors of mTORC1 and mTORC2. The study suggests possible future research directions, such as the development of novel approaches to target mTORC1 and mTORC2 in cancer and stem cells.
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