ArticleOncogene2019
Identification and characterization of two novel oncogenic mTOR mutations.
Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- The Changing Face ofFrontiers in surgery · 2020Pooled it
- RagC and Map4K3 deficiency in high-grade gliomas drives proliferation and modulates mTORC1-dependent cellular functions.Journal of neuropathology and experimental neurology · 2026Article
- LncRNAFrontiers in endocrinology · 2026Article
- Anaplastic thyroid cancer: Genetic roles, targeted therapy, and immunotherapy.Genes & diseases · 2025Review
- Branched-chain amino acid and cancer: metabolism, immune microenvironment and therapeutic targets.Journal of translational medicine · 2025Review
- Case Report: Late simultaneous metastasis of renal clear cell carcinoma to the ampulla and breast.Frontiers in oncology · 2025Article
- The Interlinking Metabolic Association between Type 2 Diabetes Mellitus and Cancer: Molecular Mechanisms and Therapeutic Insights.Diagnostics (Basel, Switzerland) · 2024Review
- LncRNA GAS8-AS1 dinucleotide genetic variantEndocrine · 2024Article
- Therapeutic advances of targeting receptor tyrosine kinases in cancer.Signal transduction and targeted therapy · 2024Review
- The mTORC2 signaling network: targets and cross-talks.The Biochemical journal · 2024Review
- Oncogenic MTOR Signaling Axis Compensates BTK Inhibition in a Chronic Lymphocytic Leukemia Patient with Richter Transformation: A Case Report and Review of the Literature.Acta haematologica · 2024Review
- The multifaced role and therapeutic regulation of autophagy in ovarian cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Review
- Review
- Papillary Thyroid Cancer and aJournal of the Endocrine Society · 2022Article
- Regulation and metabolic functions of mTORC1 and mTORC2.Physiological reviews · 2021Review
- Review
- Article
- Mutational drivers of cancer cell migration and invasion.British journal of cancer · 2021Review
- Akt1 genetic variants confer increased susceptibility to thyroid cancer.Endocrine connections · 2020Article
- Contemporary Management of Anaplastic Thyroid Cancer.Current treatment options in oncology · 2020Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Mammalian target of rapamycin (mTOR) signaling is often aberrantly activated, particularly when genetically altered, in human cancers. mTOR inhibitors targeting the activated mTOR signaling are highly promising anti-cancer drugs. Knowing the activating genetic change in mTOR can help guide the use of mTOR inhibitors for cancer treatment. This study was conducted to identify and characterize novel oncogenic mTOR mutations that can potentially be therapeutic targets in human cancer. We sequenced 30 exons of the mTOR gene in 12 thyroid cancer cell lines, 3 melanoma cell lines, 20 anaplastic thyroid cancer (ATC) tumors, and 23 melanoma tumors and functionally characterized the identified novel mTOR mutations in vitro and in vivo. We identified a novel point mutation A1256G in ATC cell line and G7076A in melanoma tumor in exon 9 and exon 51 of the mTOR gene, respectively. Over-expression of the corresponding mTOR mutants H419R and G2359E created through induced mutagenesis showed markedly elevated protein kinase activities associated with the activation of mTOR/p70S6K signaling in HEK293T cells. Stable expression of the two mTOR mutants in NIH3T3 cells strongly activated the mTOR/p70S6K signaling pathway and induced morphologic transformation, cell focus formation, anchorage-independent cell growth, and invasion. Inoculation of these mutant-expressing cells in athymic nude mice induced rapid tumor development, showing their driving oncogenicity. We also demonstrated that transfection with the novel mutants conferred cells high sensitivities to the mTOR inhibitor temsirolimus. We speculate that human cancers harboring these mTOR mutations, such as ATC and melanoma, may be effectively treated with inhibitors targeting mTOR.
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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.