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Related Concept Videos

mTOR Signaling and Cancer Progression03:03

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...
mTOR Signaling and Cancer Progression03:03

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/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...

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Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
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The mTOR pathway in hepatic malignancies.

Mamatha Bhat1, Nahum Sonenberg, Gregory J Gores

  • 1Division of Gastroenterology, McGill University Health Centre, Montreal, Canada.

Hepatology (Baltimore, Md.)
|February 15, 2013
PubMed
Summary

The mechanistic/mammalian target of rapamycin (mTOR) pathway is crucial in liver cancer. This review explores mTOR

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • The mechanistic/mammalian target of rapamycin (mTOR) pathway is integral to cellular processes and implicated in various cancers.
  • mTOR pathway dysregulation is observed in up to 50% of hepatocellular carcinoma (HCC) cases, highlighting its role in liver cancer initiation.
  • While metformin and existing mTOR inhibitors show some promise, complete pathway suppression remains a challenge.

Purpose of the Study:

  • To review the complex biochemistry of the mTOR pathway.
  • To elucidate the role of mTOR in hepatic carcinogenesis, focusing on hepatocellular carcinoma and cholangiocarcinoma.
  • To discuss therapeutic strategies targeting the mTOR pathway in liver malignancies.

Main Methods:

  • Literature review of preclinical and clinical studies.

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Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
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  • Analysis of biochemical mechanisms underlying mTOR signaling.
  • Examination of epidemiological data on metformin and liver cancer.

    • Main Results:

    • The mTOR pathway is a significant driver in hepatocellular carcinoma development.
    • Metformin's ability to inhibit mTOR via AMPK activation suggests a role in decreasing liver carcinogenesis.
    • Current mTOR inhibitors have limitations; active site inhibitors offer potential for complete pathway suppression.
    • The role of mTOR in cholangiocarcinoma progression requires further investigation.

    Conclusions:

    • The mTOR pathway is a critical target for therapeutic intervention in liver cancer.
    • Further research into novel mTOR inhibitors is warranted for improved efficacy in treating hepatic malignancies.
    • Understanding mTOR's specific roles in different liver cancer subtypes is essential for personalized treatment strategies.