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mTOR signalling and cellular metabolism are mutual determinants in cancer.

Dirk Mossmann, +2 more
- 01 Dec 2018 - 
- Vol. 18, Iss: 12, pp 744-757
TLDR
The interdependencies of mTOR signalling and metabolism pathways in cancer and how metabolic reprogramming in response to changes in m TOR signalling and vice versa can sustain tumorigenicity are discussed.
Abstract
Oncogenic signalling and metabolic alterations are interrelated in cancer cells. mTOR, which is frequently activated in cancer, controls cell growth and metabolism. mTOR signalling regulates amino acid, glucose, nucleotide, fatty acid and lipid metabolism. Conversely, metabolic inputs, such as amino acids, activate mTOR. In this Review, we discuss how mTOR signalling rewires cancer cell metabolism and delineate how changes in metabolism, in turn, sustain mTOR signalling and tumorigenicity. Several drugs are being developed to perturb cancer cell metabolism. However, their efficacy as stand-alone therapies, similar to mTOR inhibitors, is limited. Here, we discuss how the interdependence of mTOR signalling and metabolism can be exploited for cancer therapy.

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Erratum: The PI3K/AKT Pathway as a Target for Cancer Treatment

TL;DR: Several drugs targeting PI3K/ATK are currently in clinical trials, alone or in combination, in both solid tumors and hematologic malignancies as mentioned in this paper, and these drugs are the focus of this review.
Journal ArticleDOI

mTOR signaling pathway and mTOR inhibitors in cancer: progress and challenges

TL;DR: The purpose of this review is to introduce the role of mTOR signaling pathway on apoptosis, autophagy, growth, and metabolism of tumor cells, and to introduced the research progress of m TOR inhibitors in the tumor field.
Journal ArticleDOI

mTOR Signaling in Cancer and mTOR Inhibitors in Solid Tumor Targeting Therapy

TL;DR: Although monotherapy and combination therapy with mTOR inhibitors have been extensively applied in preclinical and clinical trials in various cancer types, innovative therapies with better efficacy and less drug resistance are still in great need, and new biomarkers and deep sequencing technologies will facilitate these mTOR targeting drugs benefit the cancer patients in personalized therapy.
Journal ArticleDOI

Metabolic coordination of T cell quiescence and activation.

TL;DR: It is proposed that immunological cues and nutrients license and tune metabolic programmes and signalling networks that communicate in a bidirectional manner to promote quiescence exit and how cell-extrinsic factors, such as nutrients and regulatory T cells, directly and indirectly balance quiescent and activation programmes in conventional T cells.
Journal ArticleDOI

The role of ubiquitination in tumorigenesis and targeted drug discovery

TL;DR: The latest progress in understanding the substrates for ubiquitination and their special functions in tumor metabolism regulation, TME modulation and CSC stemness maintenance are summarized and potential therapeutic targets for cancer are reviewed.
References
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Journal ArticleDOI

Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation

TL;DR: It is proposed that the metabolism of cancer cells, and indeed all proliferating cells, is adapted to facilitate the uptake and incorporation of nutrients into the biomass needed to produce a new cell.
Journal ArticleDOI

mTOR Signaling in Growth, Metabolism, and Disease.

Robert A. Saxton, +1 more
- 09 Mar 2017 - 
TL;DR: Recent advances in understanding of mTOR function, regulation, and importance in mammalian physiology are reviewed and how the mTOR signaling network contributes to human disease is highlighted.
Journal ArticleDOI

The Emerging Hallmarks of Cancer Metabolism

TL;DR: This Perspective has organized known cancer-associated metabolic changes into six hallmarks: deregulated uptake of glucose and amino acids, use of opportunistic modes of nutrient acquisition, useof glycolysis/TCA cycle intermediates for biosynthesis and NADPH production, increased demand for nitrogen, alterations in metabolite-driven gene regulation, and metabolic interactions with the microenvironment.
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TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling

TL;DR: It is shown that TSC1–TSC2 inhibits the p70 ribosomal protein S6 kinase 1 and activates the eukaryotic initiation factor 4E binding protein 1 (4E-BP1, an inhibitor of translational initiation) and these functions are mediated by inhibition of the mammalian target of rapamycin (mTOR).
Journal ArticleDOI

Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Bα

TL;DR: In this paper, a protein kinase that phosphorylates PKB α at Thr308 and increases its activity over 30-fold was found to play a key role in mediating the activation of PKB by insulin and growth factors.
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