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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.
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Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
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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...
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Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
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The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
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Related Experiment Video

Updated: Jul 6, 2025

A Patient-Derived Xenograft Model for Venous Malformation
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mTOR Pathway Substrates Present High Activation in Vascular Malformations and Significantly Decrease with Age.

Jakub Kopeć1, Elżbieta Sałacińska-Łoś1, Magdalena Orzechowska2

  • 1Pediatric Surgery and Oncology Department, Medical University of Łódź, 90-419 Lodz, Poland.

Diagnostics (Basel, Switzerland)
|January 11, 2024
PubMed
Summary

Vascular malformations show higher mammalian target of rapamycin (mTOR) pathway substrate activation than healthy tissue. This suggests mTOR

Keywords:
lymphatic malformationmTORrapamycinsirolimusvascular anomaliesvenus malformation

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Area of Science:

  • Vascular biology and cell signaling.
  • Dermatology and medical research.

Background:

  • Vascular anomalies cause significant patient morbidity and are challenging to treat.
  • The mammalian target of rapamycin (mTOR) pathway is implicated in vascular malformation development.
  • Specific mechanisms of mTOR dysregulation in these conditions remain unclear.

Purpose of the Study:

  • To investigate the activation status of key mammalian target of rapamycin (mTOR) pathway substrates.
  • To assess the role of mTOR signaling in the pathogenesis of vascular anomalies.

Main Methods:

  • Histopathological analysis of tissue samples from 82 patients with various vascular malformations and healthy controls.
  • Immunohistochemical staining for p70 S6 Kinase, 4EBP1, and p-4EBP1.
  • Statistical analysis using R packages (FactoMineR, factoextra).

Main Results:

  • Vascular malformations exhibited significantly higher mTOR substrate activation compared to healthy tissues.
  • Elevated p-4EBP1 expression was noted in females with malformations.
  • mTOR substrate expression decreased with increasing age.

Conclusions:

  • Increased mTOR substrate expression in vascular malformations supports its role in abnormal vascular development.
  • Age-dependent changes in mTOR signaling indicate potential for age-specific therapeutic strategies.
  • Understanding mTOR pathway activation offers a potential therapeutic target for personalized medicine approaches.