What is the role of mTOR in cancer?

The mammalian or mechanistic target of rapamycin (mTOR) pathway plays a crucial role in regulation of cell survival, metabolism, growth and protein synthesis in response to upstream signals in both normal physiological and pathological conditions, especially in cancer.

Does mTOR cause cancer?

Abstract. Mammalian target of rapamycin (mTOR) regulates cell proliferation, autophagy, and apoptosis by participating in multiple signaling pathways in the body. Studies have shown that the mTOR signaling pathway is also associated with cancer, arthritis, insulin resistance, osteoporosis, and other diseases.

What happens if the mTOR pathway is inhibited?

The inhibition of mTOR blocks the binding of the accessory protein raptor (regulatory-associated protein of mTOR) to mTOR, but that is necessary for downstream phosphorylation of S6K1 and 4EBP1. As a consequence, S6K1 dephosphorylates, which reduces protein synthesis and decreases cell mortality and size.

Is mTOR an oncogene or tumor suppressor?

mTORC1 has been shown to directly phosphorylate STAT3 at Ser727 [63] and to be partially sensitive to rapamycin treatment. STAT3 is classed as an oncogene and plays a pivotal role in carcinogenesis and tumour formation.

Is mTOR a tumor suppressor?

Therefore, although mTORC1 activation contributes to tumor development and progression, it can also have tumor-suppressive effects because of feedback mechanisms.

What cancer does rapamycin treat?

Rapamycin is approved to treat renal cancer and is in clinical trials to treat various other cancers, but the molecular determinants of drug response are unknown. Preclinical data show that loss of the tumour suppressor PTEN sensitizes tumours to the inhibition of mammalian target of rapamycin (mTOR).

What can mTOR inhibition cause?

Caloric restriction achieves mTOR inhibition through two pathways: decreased PI3K activity and increased AMPK activity (Figure 2). Cells in low energy states (calorically restricted) have low PI3K activity, lowering Akt activity, which then lowers mTORC1 via inhibition by Tsc1/2 (Figure 3).

Does fasting inhibit mTOR?

Because mTOR is a nutrient-sensing pathway, it can be deactivated by fasting and severe calorie restriction (CR), which exert metabolic effect that are somewhat similar, but not identical, to those of rapamycin42.

What is mTOR mutation?

Mutations in the MTOR gene cause a neurological disorder called Smith-Kingsmore syndrome. Individuals with this condition typically have a head that is larger than normal (macrocephaly), intellectual disability, and seizures.

Can rapamycin cause cancer?

Although rapamycin and its analogs are now approved by the FDA for treatment of cancer and lymphomas, the rumors that these drugs may cause cancer persist. To my knowledge, no study has shown that mTOR inhibitors cause cancer.

Does metformin inhibit mTOR?

Metformin and resveratrol inhibit mTOR through upstream pathways, inhibiting the mitochondrial complex I activity and increasing AMPK respectively.

Why does mTOR cause aging?

The inhibition of mTORC1 slows aging by an increased in autophagy, favoring the elimination of misfolded proteins and impaired organelles such as mitochondria, avoiding its accumulation, and associated with aging and different aging-related diseases such as T2DM, or Parkinson disease, or Alzheimer disease (47).