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Review

mTOR Complexes as a Nutrient Sensor for Driving Cancer Progression

1
Department of Pathology, Division of Pathological Neuroscience, Tokyo Women’s Medical University, Tokyo 162-8666, Japan
2
Ludwig Institute for Cancer Research, University of California San Diego, La Jolla, CA 92093, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(10), 3267; https://doi.org/10.3390/ijms19103267
Received: 16 September 2018 / Revised: 14 October 2018 / Accepted: 14 October 2018 / Published: 21 October 2018
(This article belongs to the Special Issue mTOR in Human Diseases)
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. View Full-Text
Keywords: mTOR complex; metabolic reprogramming; cancer; microenvironment; nutrient sensor mTOR complex; metabolic reprogramming; cancer; microenvironment; nutrient sensor
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MDPI and ACS Style

Harachi, M.; Masui, K.; Okamura, Y.; Tsukui, R.; Mischel, P.S.; Shibata, N. mTOR Complexes as a Nutrient Sensor for Driving Cancer Progression. Int. J. Mol. Sci. 2018, 19, 3267. https://doi.org/10.3390/ijms19103267

AMA Style

Harachi M, Masui K, Okamura Y, Tsukui R, Mischel PS, Shibata N. mTOR Complexes as a Nutrient Sensor for Driving Cancer Progression. International Journal of Molecular Sciences. 2018; 19(10):3267. https://doi.org/10.3390/ijms19103267

Chicago/Turabian Style

Harachi, Mio, Kenta Masui, Yukinori Okamura, Ryota Tsukui, Paul S. Mischel, and Noriyuki Shibata. 2018. "mTOR Complexes as a Nutrient Sensor for Driving Cancer Progression" International Journal of Molecular Sciences 19, no. 10: 3267. https://doi.org/10.3390/ijms19103267

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