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AnyGenes

mTOR Pathway  mTOR Pathway

mTOR pathway through two distinct protein complexes mTORC1 and mTORC2, coordinates eukaryotic cell growth and metabolism with environmental inputs including nutrients and growth factors (1). mTOR was also shown to be regulated by other external stresses, such as oxygen deprivation (hypoxia), radiation, high salt concentration, DNA topoisomerase inhibitors, and histone deacetylase inhibitors (6).

The distinct roles of mTOR were identified in gene transcription, protein synthesis, tissue regeneration and repair, oxidative stress, immunity, aging, and cell death that include autophagy and apoptosis, insulin resistance, adipogenesis, and T-lymphocyte activation (2,4).

mTOR-Pathway-mTORC2.png

 
The structures, regulatory mechanism and functions of mTORC2 (4)
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mTOR-Signaling-mTORC1

The regulatory mechanism and function of the mammalian target of rapamycin complex 1 (mTORC1). (A) The structures and regulatory mechanism of mTORC1. (B) The downstream functions of mTORC1 (4).

Signaling Pathway  mTOR Signaling Pathway and diseases

The de-regulated activity of mTOR is involved in many pathophysiological conditions, such as aging, Alzheimer’s disease, obesity, diabetic complications, pulmonary hypertension, cardiovascular diseases, neurodegeneration, and cancer (2,3,7).
Through diverse mechanisms (promotion of growth factor receptor signaling, angiogenesis, glyolytic metabolism, lipid metabolism, cancer cell migration, and suppression of autophagy), recent studies suggest that mTOR signaling pathway plays an essential role in the regulation of tumor cell motility, invasion and metastasis (5). Hence, mTOR is a promising target for cancer therapy by developing mTOR inhibitors (7).
(1)  Saxton RA  et  Sabatini  DM. mTOR  Signaling in  Growth,  Metabolism, and  Disease. Cell. (2017)9;168(6):960-976.
(2)   Das A  et  al. mTOR  Signaling  in  Cardiometabolic  Disease,  Cancer,  and  Aging. Oxid Med Cell Longev. (2017).
(3)  Chamcheu JC et al. Role and Therapeutic Targeting of  the PI3K/Akt/mTOR Signaling Pathway in Skin Cancer: A Review of Current Status and Future Trends on Natural and Synthetic  Agents  Therapy. Cells. (2019)31;8(8).
(4)    Wei X  et  al.  Roles  of  mTOR  Signaling  in  Tissue  Regeneration. Cells. (2019)12;8(9).
(5)  Kwasnicki A et al. Involvement of mTOR signaling pathways in regulating growth and dissemination  of  metastatic  brain  tumors  via  EMT. Anticancer Res. (2015);35(2):689-96.
(6)  Paquette  M  e t  al.  mTOR  Pathways  in  Cance r  and  Autophagy. Cancers (Basel). (2018);10(1).
(7) Hua H  e t  al.  Targeting  mTOR  for  cancer  therapy.  J Hematol Oncol. (2019);12(1):71.
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