Related Experiment Video
Updated: May 20, 2026
07:38
Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
Published on: June 6, 2025
PI3K/mTOR signaling pathways in medulloblastoma
Avinash L Mohan1, Marissa D Friedman, D Ryan Ormond
1Department of Neurosurgery, New York Medical College, Valhalla, NY, USA.
Anticancer Research
|July 31, 2012
Summary
Targeting the mammalian target of rapamycin (mTOR) pathway shows promise for treating pediatric medulloblastoma. Inhibitors like rapamycin and pp242 suppressed tumor cell proliferation and migration, offering new therapeutic strategies.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Medulloblastoma is the most common pediatric malignant brain tumor.
- Dysregulation of sonic hedgehog (SHH) and insulin growth factor (IGF) pathways activates mammalian target of rapamycin (mTOR).
- mTOR functions through two distinct complexes: mTORC1 and mTORC2.
Purpose of the Study:
- To investigate the role of the mTOR pathway in medulloblastoma development.
- To evaluate mTOR inhibitors as potential therapeutic agents for medulloblastoma.
Main Methods:
- Treatment of medulloblastoma cells with mTORC1 inhibitor (rapamycin) and a combined mTORC1/2 inhibitor (pp242).
- Assessment of key protein expressions including pERK, p70S6K, and pAKT(Ser473).
- Analysis of cell proliferation, cell cycle progression (EdU incorporation), and cell migration.
Main Results:
- Rapamycin initially down-regulated pERK but led to ERK activation upon prolonged treatment; it reduced p70S6K and pAKT(Ser473) phosphorylation.
- Both rapamycin and pp242 suppressed medulloblastoma cell proliferation by inhibiting S-phase entry, with pp242 showing greater efficacy.
- Rapamycin treatment inhibited medulloblastoma cell migration.
Conclusions:
- The mTOR pathway is implicated in medulloblastoma pathogenesis.
- Targeting the mTOR pathway with inhibitors represents a potential therapeutic strategy for medulloblastoma.
Related Concept Videos
01:22PI3K/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...
03:03mTOR 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...
The mTOR pathway or the...
03:03mTOR 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...
The mTOR pathway or the...
01:19Interactions 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...
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...
01:20The JAK-STAT Signaling Pathway
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...