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mTOR in Metabolism and Cancer

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (30 March 2024) | Viewed by 3080

Special Issue Editor


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Guest Editor
Department of Molecular Medicine, UT Health Science Center San Antonio, San Antonio, TX 78229, USA
Interests: cancer; metabolism; mRNA translation; mRNA degradation; mTOR
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Mechanistic target of rapamycin (mTOR) integrates extracellular and intracellular signals (e.g., growth factors, insulin, nutrients, and oxygen) to stimulate anabolism, including protein and lipid synthesis, and bolster cellular growth and proliferation while suppressing autophagy. mTOR forms two distinct complexes, mTOR complex 1 (mTORC1) and 2 (mTORC2), which differ in their composition, downstream targets, regulation, and sensitivity to the naturally occurring allosteric mTOR inhibitor rapamycin. Dysregulation of the mTOR signaling pathway frequently accompanies diseases characterized by perturbations in energy metabolism and cell growth, such as cancer and metabolic syndrome. The first generation of mTOR inhibitors, rapamycin and its analogs, have been used for the treatment of several types of cancer with modest therapeutic effects. Chronic rapamycin significantly increases lifespan in model organisms with better health indicators. A new generation of ATP-competitive inhibitors that directly target the mTOR catalytic domain show potent and comprehensive inhibition and are currently being tested in clinics. The major clinical benefits of mTOR inhibition will likely be in the prevention or management of age-related diseases such as cancer and metabolic syndrome and its associated complications, resulting in late-life morbidity compression.

Continuing from the previous Issue, this Special Issue will cover a selection of recent research topics and current review articles in the field of the mTOR pathway and its impacts on metabolism and cancers.

Dr. Masahiro Morita
Guest Editor

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Keywords

  • mTOR
  • rapamycin
  • inhibitor
  • cancer
  • metabolic syndrome
  • aging
  • mRNA translation
  • 4E-BP
  • S6K
  • autophagy

Published Papers (2 papers)

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Research

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21 pages, 5010 KiB  
Article
Regulation of Benzo[a]pyrene-Induced Hepatic Lipid Accumulation through CYP1B1-Induced mTOR-Mediated Lipophagy
by Kyung-Bin Bu, Min Kim, Min Kyoung Shin, Seung-Ho Lee and Jung-Suk Sung
Int. J. Mol. Sci. 2024, 25(2), 1324; https://doi.org/10.3390/ijms25021324 - 22 Jan 2024
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Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is caused by lipid accumulation within the liver. The pathogenesis underlying its development is poorly understood. Benzo[a]pyrene (B[a]P) is a polycyclic aromatic hydrocarbon and a group 1 carcinogen. The aryl hydrocarbon receptor activation by B[a]P induces cytochrome [...] Read more.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is caused by lipid accumulation within the liver. The pathogenesis underlying its development is poorly understood. Benzo[a]pyrene (B[a]P) is a polycyclic aromatic hydrocarbon and a group 1 carcinogen. The aryl hydrocarbon receptor activation by B[a]P induces cytochrome P450 (CYP) enzymes, contributing to hepatic lipid accumulation. However, the molecular mechanism through which the B[a]P-mediated induction of CYP enzymes causes hepatic lipid accumulation is unknown. This research was conducted to elucidate the role of CYP1B1 in regulating B[a]P-induced lipid accumulation within hepatocytes. B[a]P increased hepatic lipid accumulation, which was mitigated by CYP1B1 knockdown. An increase in the mammalian target of rapamycin (mTOR) by B[a]P was specifically reduced by CYP1B1 knockdown. The reduction of mTOR increased the expression of autophagic flux-related genes and promoted phagolysosome formation. Both the expression and translocation of TFE3, a central regulator of lipophagy, were induced, along with the expression of lipophagy-related genes. Conversely, enhanced mTOR activity reduced TFE3 expression and translocation, which reduced the expression of lipophagy-related genes, diminished phagolysosome production, and increased lipid accumulation. Our results indicate that B[a]P-induced hepatic lipid accumulation is caused by CYP1B1-induced mTOR and the reduction of lipophagy, thereby introducing novel targets and mechanisms to provide insights for understanding B[a]P-induced MASLD. Full article
(This article belongs to the Special Issue mTOR in Metabolism and Cancer)
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Review

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17 pages, 2515 KiB  
Review
mTOR: Its Critical Role in Metabolic Diseases, Cancer, and the Aging Process
by Sulaiman K. Marafie, Fahd Al-Mulla and Jehad Abubaker
Int. J. Mol. Sci. 2024, 25(11), 6141; https://doi.org/10.3390/ijms25116141 - 2 Jun 2024
Cited by 1 | Viewed by 1543
Abstract
The mammalian target of rapamycin (mTOR) is a pivotal regulator, integrating diverse environmental signals to control fundamental cellular functions, such as protein synthesis, cell growth, survival, and apoptosis. Embedded in a complex network of signaling pathways, mTOR dysregulation is implicated in the onset [...] Read more.
The mammalian target of rapamycin (mTOR) is a pivotal regulator, integrating diverse environmental signals to control fundamental cellular functions, such as protein synthesis, cell growth, survival, and apoptosis. Embedded in a complex network of signaling pathways, mTOR dysregulation is implicated in the onset and progression of a range of human diseases, including metabolic disorders such as diabetes and cardiovascular diseases, as well as various cancers. mTOR also has a notable role in aging. Given its extensive biological impact, mTOR signaling is a prime therapeutic target for addressing these complex conditions. The development of mTOR inhibitors has proven advantageous in numerous research domains. This review delves into the significance of mTOR signaling, highlighting the critical components of this intricate network that contribute to disease. Additionally, it addresses the latest findings on mTOR inhibitors and their clinical implications. The review also emphasizes the importance of developing more effective next-generation mTOR inhibitors with dual functions to efficiently target the mTOR pathways. A comprehensive understanding of mTOR signaling will enable the development of effective therapeutic strategies for managing diseases associated with mTOR dysregulation. Full article
(This article belongs to the Special Issue mTOR in Metabolism and Cancer)
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