ArticleThe EMBO journal2018
Tuberous sclerosis complex is required for tumor maintenance in MYC-driven Burkitt's lymphoma.
Article in The EMBO journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 20 citations in OpenAlex.
- Genome-wide in vivo CRISPR screens identify GATOR1 complex as a tumor suppressor in Myc-driven lymphoma.Nature communications · 2025Article
- Integrating Network Pharmacology andCombinatorial chemistry & high throughput screening · 2025Article
- The Role of Emodin in the Treatment of Bladder Cancer Based on Network Pharmacology and Experimental Verification.Combinatorial chemistry & high throughput screening · 2024Article
- Review
- Identification of in vivo roles of ErbB4-JMa and its direct nuclear signaling using a novel isoform-specific knock out mouse.Scientific reports · 2022Article
- Metabolic adaptation of lymphocytes in immunity and disease.Immunity · 2022Review
- Rapamycin and dexamethasone during pregnancy prevent tuberous sclerosis complex-associated cystic kidney disease.JCI insight · 2020Article
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The tuberous sclerosis complex (TSC) 1/2 is a negative regulator of the nutrient-sensing kinase mechanistic target of rapamycin complex (mTORC1), and its function is generally associated with tumor suppression. Nevertheless, biallelic loss of function of TSC1 or TSC2 is rarely found in malignant tumors. Here, we show that TSC1/2 is highly expressed in Burkitt's lymphoma cell lines and patient samples of human Burkitt's lymphoma, a prototypical MYC-driven cancer. Mechanistically, we show that MYC induces TSC1 expression by transcriptional activation of the TSC1 promoter and repression of miR-15a. TSC1 knockdown results in elevated mTORC1-dependent mitochondrial respiration enhanced ROS production and apoptosis. Moreover, TSC1 deficiency attenuates tumor growth in a xenograft mouse model. Our study reveals a novel role for TSC1 in securing homeostasis between MYC and mTORC1 that is required for cell survival and tumor maintenance in Burkitt's lymphoma. The study identifies TSC1/2 inhibition and/or mTORC1 hyperactivation as a novel therapeutic strategy for MYC-driven cancers.
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