Name: how mtor drives cell growth in cancer
Uploaded: 2021-04-07T12:12:02.000Z
Duration: 3 min 3 s
Channel: JoVE

All eukaryotic cells must regulate their growth depending on the cues from their environment.
Certain genes, such as the mechanistic target of rapamycin, or mTOR, respond to various factors to regulate fundamental cellular processes, including the availability of nutrients, growth factors, and cellular stress.
mTOR is a large protein kinase of mammalian cells that exists in two functionally distinct multiprotein complexes - mTOR complex 1 or mTORC1 and mTOR complex 2 or mTORC2.
Amongst an immensely complex mTOR signaling network, the PI(3)K/AKT/mTOR pathway plays a crucial role in cell growth control.
Upon stimulation by binding insulin or insulin-like growth factors, the receptor tyrosine kinases on the cell surface activate the downstream signaling molecule- phosphatidylinositol 3-kinase or PI(3)K.
Active PI(3)K generates phosphatidylinositol 3,4,5-trisphosphate or PIP3, which enables 3-phosphoinositide-dependent kinase 1 or PDK1 to phosphorylate and activate another protein called AKT.
Active AKT protein, in turn, phosphorylates and inhibits the activity of the growth-suppressing, tuberin-hamartin complex or TSC complex.
TSC complex has a GTPase-activating&#160; activity. In its acti

mtor signaling and cancer progression

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the PI3K/AKT/mTOR signaling pathway begins with the growth-factor-induced phosphorylation of a specific cell-surface receptor. The phosphorylated receptor transmits signals that result in the activation of downstream protein kinases&#8212; PI3K, Akt, and mTOR complex 1 or mTORC1.
Upon activation, mTORC1 upregulates protein synthesis mainly through the phosphorylation of the eukaryotic initiation factor 4E-binding protein 1 or 4EBP1 and the p70 ribosomal S6 kinase 1 or S6K1. Via activation of S6K1, mTORC1 also regulates the activity of transcription factor - sterol responsive element binding protein or SREBP, which further regulates the synthesis of lipids in a growing cell. In addition, S6K1 is also involved in the activation of carbamoyl-phosphate synthetase (CAD), which plays a critical role in the de novo pyrimidine synthesis pathway.
Besides synthesis of the macromolecules, mTORC1 has also been shown to regulate mitochondrial metabolism and biosynthesis. It facilitates tumor cell growth by shifting glucose metabolism to glycolysis instead of oxidative phosphorylation, a process called the Warburg effect, to help the tumor cells generate the energy needed for their rapid growth and proliferation.
In the absence of essential nutrients, cells activate autophagy to supply basic components such as amino acids to the cellular machinery. Inhibition of mTORC1 has been shown to increase autophagy, whereas stimulation of mTORC1 reduces autophagy.
Due to its varied roles in cellular functions, deregulation in mTOR signaling has not only been implicated in the progression of cancer but also several other diseases, including, aging and diabetes.&#160;

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a ...

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JoVE Core

Molecular Biology

Unit 2

Cancer

KEY TERMS AND CONCEPTS

how mtor drives cell growth in cancer

mTOR signaling helps control cell growth by balancing building processes and breakdown processes. mTOR stands for mammalian target of rapamycin. It was discovered in 1994 because it binds directly to rapamycin. Its name also comes from a yeast protein called TOR.

In mammalian cells, the mTOR protein complex responds to environmental cues such as nutrients and growth factors. It supports anabolic processes, which are the cell’s building steps. These include the synthesis of proteins, lipids, and nucleotides. It also helps regulate catabolic processes, including autophagy, which is the cell’s recycling system.

The PI3K/AKT/mTOR signaling pathway starts when a growth factor triggers phosphorylation of a specific receptor on the cell surface. Phosphorylation is the addition of a phosphate group that helps pass along a signal. The activated receptor then sends signals through PI3K, Akt, and mTOR complex 1, or mTORC1. When mTORC1 is active, it increases protein synthesis by acting on 4EBP1 and p70 ribosomal S6 kinase 1, or S6K1.

mTORC1 also supports lipid production and DNA building. Through S6K1, it helps control SREBP, a transcription factor that regulates lipid synthesis in a growing cell. S6K1 also helps activate CAD, which is important for de novo pyrimidine synthesis. mTORC1 can also affect mitochondrial metabolism and biosynthesis.

In cancer cells, mTORC1 can help growth by shifting glucose use toward glycolysis instead of oxidative phosphorylation. This shift is known as the Warburg effect. It gives tumor cells the energy they need for rapid growth and division. When nutrients are missing, cells can activate autophagy to supply basic materials such as amino acids. Inhibition of mTORC1 increases autophagy, while stimulation of mTORC1 reduces it.

Because mTOR affects so many cell functions, its disruption has been linked to cancer progression. It has also been linked to aging and diabetes. Studying the mTOR pathway helps explain how cells decide between growth, recycling, and energy use.

How mTOR Drives Cell Growth in Cancer

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mTOR signaling helps control cell growth by balancing building processes and breakdown processes. mTOR stands for mammalian target of rapamycin. It was discovered in 1994 because it binds directly to rapamycin. Its name also comes from a yeast protein called TOR. In mammalian cells, the mTOR protein complex responds to environmental cues such as nutrients and growth factors. It supports anabolic processes, which are the cell’s building steps. These include the synthesis of proteins, lipids,...

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How Tumor Suppressor Genes Prevent Cancer

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key terms and concepts

Learn how mTOR signaling controls cell growth, protein synthesis, autophagy, and the Warburg effect, and why its disruption is linked to cancer.

How mTOR Drives Cell Growth in Cancer | JoVE K12

molecular biology

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How mTOR Drives Cell Growth in Cancer

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