ArticleScience advances2018
ETV7 is an essential component of a rapamycin-insensitive mTOR complex in cancer.
Article in Science advances, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 132 citations in OpenAlex.
- Review
- Recent Advances in Benzimidazole-Triazole Hybrids for Single- and Multi-Target Protein Kinase Inhibition.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Graph Neural Networks Model Based on Atomic Hybridization for Predicting Drug Targets.Journal of chemical information and modeling · 2026Article
- mTOR signaling networks: mechanistic insights and translational frontiers in disease therapeutics.Signal transduction and targeted therapy · 2025Review
- PI3K/AKT/mTOR axis in vascular malformations: from molecular insights to targeted clinical trials.Orphanet journal of rare diseases · 2025Review
- Graph Neural Networks Model Based on Atomic Hybridization for Predicting Drug Targets.bioRxiv : the preprint server for biology · 2025Article
- Collagen Signaling via DDR1 Exacerbates Barriers to Macromolecular Drug Delivery in a 3D Model of Pancreatic Cancer Fibrosis.Small (Weinheim an der Bergstrasse, Germany) · 2025Article
- Upregulated E26 Transformation-Specific Variant Transcription Factor 7 in Oral Squamous Cell Carcinoma: Clinicopathological Correlations and Immune Regulatory Mechanisms.World journal of oncology · 2025Article
- Review
- Article
- The mTOR Signaling Pathway: Key Regulator and Therapeutic Target for Heart Disease.Biomedicines · 2025Review
- HPV-Associated Gene Signatures in Bladder Cancer: A Comprehensive Prognostic Model and its Implications in Immunotherapy.International journal of medical sciences · 2025Article
- Targeting the PI3K/AKT/mTOR pathway in lung cancer: mechanisms and therapeutic targeting.Frontiers in pharmacology · 2025Review
- Targeting mTOR Kinase with Natural Compounds: Potent ATP-Competitive Inhibition Through Enhanced Binding Mechanisms.Pharmaceuticals (Basel, Switzerland) · 2024Article
- JR-AB2-011 induces fast metabolic changes independent of mTOR complex 2 inhibition in human leukemia cells.Pharmacological reports : PR · 2024Article
- A multiprotein signaling complex sustains AKT and mTOR/S6K activity necessary for the survival of cancer cells undergoing stress.bioRxiv : the preprint server for biology · 2024Article
- Assembly of mTORC3 Involves Binding of ETV7 to Two Separate Sequences in the mTOR Kinase Domain.International journal of molecular sciences · 2024Article
- Enhancing Therapeutic Efficacy of FLT3 Inhibitors with Combination Therapy for Treatment of Acute Myeloid Leukemia.International journal of molecular sciences · 2024Review
- Sex, tissue, and mitochondrial interactions modify the transcriptional response to rapamycin in Drosophila.BMC genomics · 2024Article
- Mitigation of Breast Cancer Cells' Invasiveness via Down Regulation of ETV7, Hippo, and PI3K/mTOR Pathways by Vitamin D3 Gold-Nanoparticles.International journal of molecular sciences · 2024Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
The mechanistic target of rapamycin (mTOR) serine/threonine kinase, a critical regulator of cell proliferation, is frequently deregulated in human cancer. Although rapamycin inhibits the two canonical mTOR complexes, mTORC1 and mTORC2, it often shows minimal benefit as an anticancer drug. This is caused by rapamycin resistance of many different tumors, and we show that a third mTOR complex, mTORC3, contributes to this resistance. The ETS (E26 transformation-specific) transcription factor ETV7 interacts with mTOR in the cytoplasm and assembles mTORC3, which is independent of ETV7's transcriptional activity. This complex exhibits bimodal mTORC1/2 activity but is devoid of crucial mTORC1/2 components. Many human cancers activate mTORC3 at considerable frequency, and tumor cell lines that lose mTORC3 expression become rapamycin-sensitive. We show mTORC3's tumorigenicity in a rhabdomyosarcoma mouse model in which transgenic ETV7 expression accelerates tumor onset and promotes tumor penetrance. Discovery of mTORC3 represents an mTOR paradigm shift and identifies a novel target for anticancer drug development.
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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.