Name: mtor pathway in cancer growth
Uploaded: 2023-04-30T18:28:51.000Z
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 ...

Education

JoVE Core

Cell Biology

Unit 1

Cancer

KEY TERMS AND CONCEPTS

mtor pathway in cancer growth

mTOR signaling helps control cell growth, and changes in this pathway can support cancer progression. The mTOR protein is a key part of this signaling system. It helps cells respond to signals that tell them when to grow and divide.

The transcript focuses on how mTOR signaling connects to cancer. When this pathway is altered, it can affect the behavior of cancer cells. Understanding this link helps explain why mTOR is an important topic in cancer biology.

mTOR signaling is studied as part of the larger process of cancer progression. This pathway is one example of how internal cell signals can influence disease development. It also shows why researchers look at signaling proteins when studying cancer.

mTOR Pathway in Cancer Growth

what is cancer?

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tumor progression

Tumor Growth and Spread

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Proto-oncogenes and Cell Growth Control

Proto-oncogenes are cancer-critical genes that help control normal cell growth. They play an important role in the signals that tell cells when to grow and divide. In healthy cells, these genes support regular cell behavior. Problems can begin when a proto-oncogene changes. A changed proto-oncogene may push a cell to divide too often or at the wrong time. This shift can contribute to cancer development. This topic focuses on proto-oncogenes as one class of cancer-related genes. It shows how...

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loss of tumor suppressor gene functions

Tumor Suppressor Gene Loss in Cancer

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the ras gene

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mTOR signaling helps control cell growth, and changes in this pathway can support cancer progression. The mTOR protein is a key part of this signaling system. It helps cells respond to signals that tell them when to grow and divide. The transcript focuses on how mTOR signaling connects to cancer. When this pathway is altered, it can affect the behavior of cancer cells. Understanding this link helps explain why mTOR is an important topic in cancer biology. mTOR signaling is studied as part of...

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mouse models of cancer study

Mouse Models for Cancer Research

Mouse models for cancer research help scientists study how tumors form and grow in a living system. Mice are used because they can be matched to many human cancer features. They also allow researchers to test ideas before moving to clinical work. These models can include mice that naturally develop tumors and mice that are engineered to carry cancer-related changes. Some models are designed to mimic specific cancers, while others are used to study general tumor behavior. Together, they give...

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Lowering Cancer Risk

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cancer therapies

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Some cancers resist treatment and keep growing even after therapy. This video focuses on why that happens and how resistance changes cancer care. Treatment resistance can develop when cancer cells survive drugs that should destroy them. The cells may avoid the drug’s effects, or they may keep dividing after treatment starts. This makes the cancer harder to control. Understanding treatment-resistant cancer helps explain why some therapies work at first and then lose effect. It also shows why...

combination therapies and personalized medicine

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Personalized Cancer Treatment with Drug Combinations

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key terms and concepts

Learn how mTOR signaling helps control cell growth and how changes in this pathway can support cancer progression in cancer biology.

mTOR Pathway in Cancer Growth | JoVE K12

cell biology

JoVE Core Cell Biology illustrates complex cellular processes in easy-to-understand yet comprehensive animated video lessons. This collection focuses on the essential components and functions of cells, including organelles and membranes, cellular transport, and cell energetics. It is complemented by scientist-in-action videos that demonstrate the application of cell biology in real-world research experiments.

mTOR Pathway in Cancer Growth

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