Related Experiment Video
Updated: May 10, 2026
07:38
Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
Published on: June 6, 2025
The mTOR pathway negatively controls ATM by up-regulating miRNAs
Changxian Shen1, Peter J Houghton
1Center for Childhood Cancer and Blood Diseases, Nationwide Children's Hospital, Columbus, OH 43205, USA.
Summary
Mammalian target of rapamycin (mTOR) signaling suppresses the ataxia telangiectasia mutated (ATM) checkpoint in sarcoma by increasing microRNAs that target ATM. Inhibiting mTOR boosts ATM levels, revealing a negative feedback loop crucial for genome integrity.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The ataxia telangiectasia mutated (ATM) checkpoint is vital for maintaining genome integrity.
- Dysregulation of ATM signaling is implicated in various cancers, including childhood sarcoma.
Purpose of the Study:
- To investigate the regulatory relationship between mammalian target of rapamycin (mTOR) signaling and the ATM checkpoint in the context of sarcoma.
- To identify the molecular mechanisms by which mTOR influences ATM activity.
Main Methods:
- Utilized mouse sarcoma xenografts and cultured sarcoma cells.
- Employed pharmacological inhibition and genetic down-regulation of the mTOR pathway.
- Analyzed ATM mRNA and protein levels.
- Investigated the role of specific microRNAs (miRNAs) and signaling pathways (S6K1/2).
Main Results:
- mTOR signaling suppresses ATM in childhood sarcoma by up-regulating miRNAs (miR-18a, miR-421) that target ATM.
- Inhibition or genetic down-regulation of mTOR led to increased ATM mRNA and protein.
- mTOR Complex 1 (mTORC1) suppresses ATM through S6K1/2 signaling pathways.
- Identified a negative feedback loop between ATM and mTOR signaling.
Conclusions:
- Oncogenic growth signals may promote tumorigenesis by suppressing the ATM checkpoint via the mTOR pathway.
- Targeting the mTOR-ATM axis could offer novel therapeutic strategies for sarcoma.
Related Concept Videos
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...
01:22PI3K/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...
01:22MicroRNAs
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
01:22MicroRNAs
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA ends...
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...