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mTOR Complexes as a Nutrient Sensor for Driving Cancer Progression

Recent advancement in the field of molecular cancer research has clearly revealed that abnormality of oncogenes or tumor suppressor genes causes tumor progression thorough the promotion of intracellular metabolism. Metabolic reprogramming is one of the strategies for cancer cells to ensure their sur...

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Autores principales: Harachi, Mio, Masui, Kenta, Okamura, Yukinori, Tsukui, Ryota, Mischel, Paul S., Shibata, Noriyuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6214109/
https://www.ncbi.nlm.nih.gov/pubmed/30347859
http://dx.doi.org/10.3390/ijms19103267
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author Harachi, Mio
Masui, Kenta
Okamura, Yukinori
Tsukui, Ryota
Mischel, Paul S.
Shibata, Noriyuki
author_facet Harachi, Mio
Masui, Kenta
Okamura, Yukinori
Tsukui, Ryota
Mischel, Paul S.
Shibata, Noriyuki
author_sort Harachi, Mio
collection PubMed
description Recent advancement in the field of molecular cancer research has clearly revealed that abnormality of oncogenes or tumor suppressor genes causes tumor progression thorough the promotion of intracellular metabolism. Metabolic reprogramming is one of the strategies for cancer cells to ensure their survival by enabling cancer cells to obtain the macromolecular precursors and energy needed for the rapid growth. However, an orchestration of appropriate metabolic reactions for the cancer cell survival requires the precise mechanism to sense and harness the nutrient in the microenvironment. Mammalian/mechanistic target of rapamycin (mTOR) complexes are known downstream effectors of many cancer-causing mutations, which are thought to regulate cancer cell survival and growth. Recent studies demonstrate the intriguing role of mTOR to achieve the feat through metabolic reprogramming in cancer. Importantly, not only mTORC1, a well-known regulator of metabolism both in normal and cancer cell, but mTORC2, an essential partner of mTORC1 downstream of growth factor receptor signaling, controls cooperatively specific metabolism, which nominates them as an essential regulator of cancer metabolism as well as a promising candidate to garner and convey the nutrient information from the surrounding environment. In this article, we depict the recent findings on the role of mTOR complexes in cancer as a master regulator of cancer metabolism and a potential sensor of nutrients, especially focusing on glucose and amino acid sensing in cancer. Novel and detailed molecular mechanisms that amino acids activate mTOR complexes signaling have been identified. We would also like to mention the intricate crosstalk between glucose and amino acid metabolism that ensures the survival of cancer cells, but at the same time it could be exploitable for the novel intervention to target the metabolic vulnerabilities of cancer cells.
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spelling pubmed-62141092018-11-14 mTOR Complexes as a Nutrient Sensor for Driving Cancer Progression Harachi, Mio Masui, Kenta Okamura, Yukinori Tsukui, Ryota Mischel, Paul S. Shibata, Noriyuki Int J Mol Sci Review Recent advancement in the field of molecular cancer research has clearly revealed that abnormality of oncogenes or tumor suppressor genes causes tumor progression thorough the promotion of intracellular metabolism. Metabolic reprogramming is one of the strategies for cancer cells to ensure their survival by enabling cancer cells to obtain the macromolecular precursors and energy needed for the rapid growth. However, an orchestration of appropriate metabolic reactions for the cancer cell survival requires the precise mechanism to sense and harness the nutrient in the microenvironment. Mammalian/mechanistic target of rapamycin (mTOR) complexes are known downstream effectors of many cancer-causing mutations, which are thought to regulate cancer cell survival and growth. Recent studies demonstrate the intriguing role of mTOR to achieve the feat through metabolic reprogramming in cancer. Importantly, not only mTORC1, a well-known regulator of metabolism both in normal and cancer cell, but mTORC2, an essential partner of mTORC1 downstream of growth factor receptor signaling, controls cooperatively specific metabolism, which nominates them as an essential regulator of cancer metabolism as well as a promising candidate to garner and convey the nutrient information from the surrounding environment. In this article, we depict the recent findings on the role of mTOR complexes in cancer as a master regulator of cancer metabolism and a potential sensor of nutrients, especially focusing on glucose and amino acid sensing in cancer. Novel and detailed molecular mechanisms that amino acids activate mTOR complexes signaling have been identified. We would also like to mention the intricate crosstalk between glucose and amino acid metabolism that ensures the survival of cancer cells, but at the same time it could be exploitable for the novel intervention to target the metabolic vulnerabilities of cancer cells. MDPI 2018-10-21 /pmc/articles/PMC6214109/ /pubmed/30347859 http://dx.doi.org/10.3390/ijms19103267 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Harachi, Mio
Masui, Kenta
Okamura, Yukinori
Tsukui, Ryota
Mischel, Paul S.
Shibata, Noriyuki
mTOR Complexes as a Nutrient Sensor for Driving Cancer Progression
title mTOR Complexes as a Nutrient Sensor for Driving Cancer Progression
title_full mTOR Complexes as a Nutrient Sensor for Driving Cancer Progression
title_fullStr mTOR Complexes as a Nutrient Sensor for Driving Cancer Progression
title_full_unstemmed mTOR Complexes as a Nutrient Sensor for Driving Cancer Progression
title_short mTOR Complexes as a Nutrient Sensor for Driving Cancer Progression
title_sort mtor complexes as a nutrient sensor for driving cancer progression
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6214109/
https://www.ncbi.nlm.nih.gov/pubmed/30347859
http://dx.doi.org/10.3390/ijms19103267
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