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Amino Acid Transporters as Targets for Cancer Therapy: Why, Where, When, and How
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Amino Acid Transporters Are a Vital Focal Point in the Control of mTORC1 Signaling and Cancer

1
Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
2
Department of Medical Biology, Centre Scientifique de Monaco (CSM), 98000 Monaco, Monaco
3
CNRS, INSERM, Centre A. Lacassagne, Faculté de Médecine (IRCAN), Université Côte d’Azur, 06107 Nice, France
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(1), 23; https://doi.org/10.3390/ijms22010023
Received: 22 October 2020 / Revised: 26 November 2020 / Accepted: 27 November 2020 / Published: 22 December 2020
(This article belongs to the Special Issue Amino Acid Transporters and Signaling in Cancer)
The mechanistic target of rapamycin complex 1 (mTORC1) integrates signals from growth factors and nutrients to control biosynthetic processes, including protein, lipid, and nucleic acid synthesis. Dysregulation in the mTORC1 network underlies a wide array of pathological states, including metabolic diseases, neurological disorders, and cancer. Tumor cells are characterized by uncontrolled growth and proliferation due to a reduced dependency on exogenous growth factors. The genetic events underlying this property, such as mutations in the PI3K-Akt and Ras-Erk signaling networks, lead to constitutive activation of mTORC1 in nearly all human cancer lineages. Aberrant activation of mTORC1 has been shown to play a key role for both anabolic tumor growth and resistance to targeted therapeutics. While displaying a growth factor-independent mTORC1 activity and proliferation, tumors cells remain dependent on exogenous nutrients such as amino acids (AAs). AAs are an essential class of nutrients that are obligatory for the survival of any cell. Known as the building blocks of proteins, AAs also act as essential metabolites for numerous biosynthetic processes such as fatty acids, membrane lipids and nucleotides synthesis, as well as for maintaining redox homeostasis. In most tumor types, mTORC1 activity is particularly sensitive to intracellular AA levels. This dependency, therefore, creates a targetable vulnerability point as cancer cells become dependent on AA transporters to sustain their homeostasis. The following review will discuss the role of AA transporters for mTORC1 signaling in cancer cells and their potential as therapeutic drug targets. View Full-Text
Keywords: amino acid transporters; LAT1; SNAT2; ASCT2; xCT; mTORC1; cancer; growth factors; nutrients amino acid transporters; LAT1; SNAT2; ASCT2; xCT; mTORC1; cancer; growth factors; nutrients
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MDPI and ACS Style

Cormerais, Y.; Vučetić, M.; Parks, S.K.; Pouyssegur, J. Amino Acid Transporters Are a Vital Focal Point in the Control of mTORC1 Signaling and Cancer. Int. J. Mol. Sci. 2021, 22, 23. https://doi.org/10.3390/ijms22010023

AMA Style

Cormerais Y, Vučetić M, Parks SK, Pouyssegur J. Amino Acid Transporters Are a Vital Focal Point in the Control of mTORC1 Signaling and Cancer. International Journal of Molecular Sciences. 2021; 22(1):23. https://doi.org/10.3390/ijms22010023

Chicago/Turabian Style

Cormerais, Yann; Vučetić, Milica; Parks, Scott K.; Pouyssegur, Jacques. 2021. "Amino Acid Transporters Are a Vital Focal Point in the Control of mTORC1 Signaling and Cancer" Int. J. Mol. Sci. 22, no. 1: 23. https://doi.org/10.3390/ijms22010023

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