ArticleThe Journal of biological chemistry2013
Mutations in critical domains confer the human mTOR gene strong tumorigenicity.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 46 citations in OpenAlex.
- Genetic analysis of key players in PI3K signaling cascade of colorectal carcinoma.Scientific reports · 2026Article
- Kinase signaling cascades: an updated mechanistic landscape.Chemical science · 2025Review
- The Role of mTOR in B Cell Lymphoid Malignancies: Biologic and Therapeutic Aspects.International journal of molecular sciences · 2023Review
- Higher mTOR Expression: A Marker of Poor Outcome in Patients with de Novo AML.Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2023Article
- Clinical Implications of mTOR Expression in Papillary Thyroid Cancer-A Systematic Review.Cancers · 2023Review
- The ClinGen Brain Malformation Variant Curation Expert Panel: Rules for somatic variants in AKT3, MTOR, PIK3CA, and PIK3R2.Genetics in medicine : official journal of the American College of Medical Genetics · 2022Article
- Marker-free co-selection for successive rounds of prime editing in human cells.Nature communications · 2022Article
- Emerging Roles for Mammalian Target of Rapamycin (mTOR) Complexes in Bladder Cancer Progression and Therapy.Cancers · 2022Review
- PI3K/Akt/mTOR Pathway and Its Role in Cancer Therapeutics: Are We Making Headway?Frontiers in oncology · 2022Review
- HDAC6 Negatively Regulates miR-155-5p Expression to Elicit Proliferation by Targeting RHEB in Microvascular Endothelial Cells under Mechanical Unloading.International journal of molecular sciences · 2021Article
- UPF1 impacts on mTOR signaling pathway and autophagy in endometrioid endometrial carcinoma.Aging · 2021Article
- mTOR Signaling as a Regulator of Hematopoietic Stem Cell Fate.Stem cell reviews and reports · 2021Review
- mTOR signalling pathway - A root cause for idiopathic autism?BMB reports · 2019Review
- Article
- The lysosomal TRPML1 channel regulates triple negative breast cancer development by promoting mTORC1 and purinergic signaling pathways.Cell calcium · 2019Article
- Invitro Evaluation of Torin2 and 2, 6-Dihydroxyacetophenone in Colorectal Cancer Therapy.Pathology oncology research : POR · 2019Article
- Prevention of pancreatic acinar cell carcinoma by Roux-en-Y Gastric Bypass Surgery.Nature communications · 2018Article
- PI3K/AKT/mTOR pathway inhibitors inhibit the growth of melanoma cells with mTOR H2189Y mutations in vitro.Cancer biology & therapy · 2018Article
- PTRF suppresses the progression of colorectal cancers.Oncotarget · 2017Article
- mTOR inhibitors in urinary bladder cancer.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase that regulates cell growth, proliferation, and survival. mTOR is frequently activated in human cancers and is a commonly sought anticancer therapeutic target. However, whether the human mTOR gene itself is a proto-oncogene possessing tumorigenicity has not been firmly established. To answer this question, we mutated evolutionarily conserved amino acids, generated eight mutants in the HEAT repeats (M938T) and the FAT (W1456R and G1479N) and kinase (P2273S, V2284M, V2291I, T2294I, and E2288K) domains of mTOR, and studied their oncogenicity. On transient expression in HEK293T cells, these mTOR mutants displayed elevated protein kinase activities accompanied by activated mTOR/p70S6K signaling at varying levels, demonstrating the gain of function of the mTOR gene with these mutations. We selected P2273S and E2288K, the two most catalytically active mutants, to further examine their oncogenicity and tumorigenicity. Stable expression of the two mTOR mutants in NIH3T3 cells strongly activated mTOR/p70S6K signaling, induced cell transformation and invasion, and remarkably, caused rapid tumor formation and growth in athymic nude mice after subcutaneous inoculation of the transfected cells. This study confirms the oncogenic potential of mTOR suggested previously and demonstrates for the first time its tumorigenicity. Thus, beyond the pivotal position of mTOR to relay the oncogenic signals from the upstream phosphatidylinositol 3-kinase/Akt pathway in human cancer, mTOR is capable potentially of playing a direct role in human tumorigenesis if mutated. These results also further support the conclusion that mTOR is a major therapeutic target in human cancers.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.