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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\u2010driven cancer. Mechanistically, we show that MYC induces TSC1 expression by transcriptional activation of the TSC1 promoter and repression of miR\u201015a. TSC1 knockdown results in elevated mTORC1\u2010dependent 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\u2010driven cancers.<\/jats:p>","DOI":"10.15252\/embj.201798589","type":"journal-article","created":{"date-parts":[[2018,9,20]],"date-time":"2018-09-20T07:16:32Z","timestamp":1537427792000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Tuberous sclerosis complex is required for tumor maintenance in MYC\u2010driven Burkitt's lymphoma"],"prefix":"10.1038","volume":"37","author":[{"given":"G\u00f6tz","family":"Hartleben","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Kr\u00e4mer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heiko","family":"Schimmel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura M","family":"Zidek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Dornblut","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9","family":"Winkler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Eichwald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gertrud","family":"Kortman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8387-3653","authenticated-orcid":false,"given":"Christian","family":"Kosan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joost","family":"Kluiver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iver","family":"Petersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anke","family":"van den Berg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8336-3485","authenticated-orcid":false,"given":"Zhao\u2010Qi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6318-7210","authenticated-orcid":false,"given":"Cornelis F","family":"Calkhoven","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,9,20]]},"reference":[{"key":"BFEMBJ201798589_CR1","doi-asserted-by":"crossref","first-page":"3627","DOI":"10.1073\/pnas.94.8.3627","volume":"94","author":"NN Ahmed","year":"1997","unstructured":"Ahmed NN, Grimes HL, Bellacosa A, Chan TO, Tsichlis PN (1997) Transduction of interleukin\u20102 antiapoptotic and proliferative signals via Akt protein kinase. 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