{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T18:10:34Z","timestamp":1788631834743,"version":"build-2803163510"},"reference-count":41,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2018,11,16]],"date-time":"2018-11-16T00:00:00Z","timestamp":1542326400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"publisher","award":["IRG14-193-01"],"award-info":[{"award-number":["IRG14-193-01"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Overexpression of the MYC oncogene is a key feature of many human malignancies including Burkitt lymphoma. While MYC is widely regarded to be a promising therapeutic target, a clinically effective MYC inhibitor is still elusive. Here, we report an alternative strategy, targeting MYC indirectly through inhibition of the HSP90 machinery. We found that inhibition of HSP90 function reduces MYC expression in human Burkitt lymphoma through suppression of MYC transcription and destabilization of MYC protein, thereby diminishing the proliferation of tumor cells. Consistently, treatment of Burkitt lymphoma cell lines with HSP90 inhibitors (17-AAG or 17-DMAG) was accompanied by downregulation of canonical MYC target genes. Combination treatment with 17-DMAG and the proteasome inhibitor, MG-132, led to accumulation of MYC protein, indicating that upon HSP90 inhibition, MYC is degraded by the proteasome. Using co-immunoprecipitation, we furthermore demonstrated a direct interaction between MYC and HSP90, indicating that MYC is an HSP90 client protein in Burkitt lymphoma. Together, we report here the use of HSP90 inhibitors as an alternative approach to target the MYC oncogene and its network in Burkitt lymphoma.<\/jats:p>","DOI":"10.3390\/cancers10110448","type":"journal-article","created":{"date-parts":[[2018,11,16]],"date-time":"2018-11-16T11:48:31Z","timestamp":1542368911000},"page":"448","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Targeting the MYC Oncogene in Burkitt Lymphoma through HSP90 Inhibition"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1811-587X","authenticated-orcid":false,"given":"Candace J.","family":"Poole","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Augusta University, 1410 Laney-Walker Blvd., Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenli","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Augusta University, 1410 Laney-Walker Blvd., Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haesung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Augusta University, 1410 Laney-Walker Blvd., Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Young","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Augusta University, 1410 Laney-Walker Blvd., Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atul","family":"Lodh","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Augusta University, 1410 Laney-Walker Blvd., Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Chadli","sequence":"additional","affiliation":[{"name":"Georgia Cancer Center, Augusta University, 1410 Laney-Walker Blvd., Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Van Riggelen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Augusta University, 1410 Laney-Walker Blvd., Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,11,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.semcancer.2006.07.014","article-title":"The c-myc target gene network","volume":"16","author":"Dang","year":"2006","journal-title":"Semin. Cancer Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1146\/annurev.cellbio.16.1.653","article-title":"The myc\/max\/mad network and the transcriptional control of cell behavior","volume":"16","author":"Grandori","year":"2000","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5595","DOI":"10.1038\/sj.onc.1204595","article-title":"Translocations involving c-myc and c-myc function","volume":"20","author":"Boxer","year":"2001","journal-title":"Oncogene"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3707","DOI":"10.1200\/JCO.2000.18.21.3707","article-title":"Molecular biology of burkitt\u2019s lymphoma","volume":"18","author":"Hecht","year":"2000","journal-title":"J. Clin. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/S0003-9861(03)00294-7","article-title":"The many faces of c-myc","volume":"416","author":"Pelengaris","year":"2003","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Poole, C.J., and van Riggelen, J. (2017). Myc-master regulator of the cancer epigenome and transcriptome. Genes, 8.","DOI":"10.3390\/genes8050142"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/S1097-2765(00)80367-6","article-title":"Reversible tumorigenesis by myc in hematopoietic lineages","volume":"4","author":"Felsher","year":"1999","journal-title":"Mol. Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3081","DOI":"10.1158\/0008-5472.CAN-07-5832","article-title":"Oncogene addiction versus oncogene amnesia: Perhaps more than just a bad habit?","volume":"68","author":"Felsher","year":"2008","journal-title":"Cancer Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3077","DOI":"10.1158\/0008-5472.CAN-07-3293","article-title":"Oncogene addiction","volume":"68","author":"Weinstein","year":"2008","journal-title":"Cancer Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1038\/nrc2887","article-title":"Targeting the dynamic HSP90 complex in cancer","volume":"10","author":"Trepel","year":"2010","journal-title":"Nat. Rev. Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.coph.2008.06.015","article-title":"Targeting HSP90: Small-molecule inhibitors and their clinical development","volume":"8","author":"Taldone","year":"2008","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1042\/BJ20071640","article-title":"The HSP90 molecular chaperone: An open and shut case for treatment","volume":"410","author":"Pearl","year":"2008","journal-title":"Biochem. J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.1182\/bloodadvances.2018016048","article-title":"Activation of myc, a bona fide client of HSP90, contributes to intrinsic ibrutinib resistance in mantle cell lymphoma","volume":"2","author":"Lee","year":"2018","journal-title":"Blood Adv."},{"key":"ref_14","first-page":"105","article-title":"HSP90 inhibition increases p53 expression and destabilizes mycn and myc in neuroblastoma","volume":"38","author":"Regan","year":"2011","journal-title":"Int. J. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1158\/1535-7163.MCT-16-0848","article-title":"Inhibition of HSP90 suppresses pi3k\/akt\/mtor signaling and has antitumor activity in burkitt lymphoma","volume":"16","author":"Dalton","year":"2017","journal-title":"Mol. Cancer Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/nature01913","article-title":"A high-affinity conformation of HSP90 confers tumour selectivity on HSP90 inhibitors","volume":"425","author":"Kamal","year":"2003","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e132","DOI":"10.1038\/bcj.2013.30","article-title":"Oral administration of an HSP90 inhibitor, 17-dmag, intervenes tumor-cell infiltration into multiple organs and improves survival period for atl model mice","volume":"3","author":"Ikebe","year":"2013","journal-title":"Blood Cancer J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1182\/blood-2010-01-263756","article-title":"17-dmag targets the nuclear factor-kappab family of proteins to induce apoptosis in chronic lymphocytic leukemia: Clinical implications of HSP90 inhibition","volume":"116","author":"Hertlein","year":"2010","journal-title":"Blood"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1073\/pnas.0809669106","article-title":"Trithorax requires HSP90 for maintenance of active chromatin at sites of gene expression","volume":"106","author":"Tariq","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1124\/mol.63.4.821","article-title":"Unexpected induction of the human connexin 43 promoter by the ras signaling pathway is mediated by a novel putative promoter sequence","volume":"63","author":"Carystinos","year":"2003","journal-title":"Mol. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Lee, Y.C., Chang, W.W., Chen, Y.Y., Tsai, Y.H., Chou, Y.H., Tseng, H.C., Chen, H.L., Wu, C.C., Chang-Chien, J., and Lee, H.T. (2017). HSP90alpha mediates bmi1 expression in breast cancer stem\/progenitor cells through facilitating nuclear translocation of c-myc and ezh2. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18091986"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1111\/bjh.14275","article-title":"Dual targeting of HSP90 in childhood acute lymphoblastic leukaemia","volume":"180","author":"Diamanti","year":"2018","journal-title":"Br. J. Haematol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1038\/leu.2009.292","article-title":"Phase i study of the heat shock protein 90 inhibitor alvespimycin (kos-1022, 17-dmag) administered intravenously twice weekly to patients with acute myeloid leukemia","volume":"24","author":"Lancet","year":"2010","journal-title":"Leukemia"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1038\/nrc.2017.36","article-title":"Drugging the \u2018undruggable\u2019 cancer targets","volume":"17","author":"Dang","year":"2017","journal-title":"Nat. Rev. Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Posternak, V., and Cole, M.D. (2016). Strategically targeting myc in cancer. F1000Res., 5.","DOI":"10.12688\/f1000research.7879.1"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1007\/s00294-016-0661-8","article-title":"Epigenetic transcriptional memory","volume":"63","author":"Brickner","year":"2017","journal-title":"Curr. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"13028","DOI":"10.1073\/pnas.0701953104","article-title":"Cellular senescence is an important mechanism of tumor regression upon c-myc inactivation","volume":"104","author":"Wu","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1038\/nature03043","article-title":"Myc inactivation uncovers pluripotent differentiation and tumour dormancy in hepatocellular cancer","volume":"431","author":"Shachaf","year":"2004","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1126\/science.1071489","article-title":"Sustained loss of a neoplastic phenotype by brief inactivation of myc","volume":"297","author":"Jain","year":"2002","journal-title":"Science"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"R69","DOI":"10.1186\/gb-2003-4-10-r69","article-title":"An integrated database of genes responsive to the myc oncogenic transcription factor: Identification of direct genomic targets","volume":"4","author":"Zeller","year":"2003","journal-title":"Genome Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.4161\/cbt.8.13.8726","article-title":"Co-treatment with heat shock protein 90 inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin (dmag) and vorinostat: A highly active combination against human mantle cell lymphoma (mcl) cells","volume":"8","author":"Rao","year":"2009","journal-title":"Cancer Biol. Ther."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2445","DOI":"10.1038\/sj.onc.1210893","article-title":"HSP90 inhibition has opposing effects on wild-type and mutant p53 and induces p21 expression and cytotoxicity irrespective of p53\/atm status in chronic lymphocytic leukaemia cells","volume":"27","author":"Lin","year":"2008","journal-title":"Oncogene"},{"key":"ref_33","first-page":"2161","article-title":"P53 mutations in raji cells: Characterization and localization relative to other burkitt\u2019s lymphomas","volume":"7","author":"Duthu","year":"1992","journal-title":"Oncogene"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2879","DOI":"10.1002\/j.1460-2075.1991.tb07837.x","article-title":"P53 is frequently mutated in burkitt\u2019s lymphoma cell lines","volume":"10","author":"Farrell","year":"1991","journal-title":"EMBO J."},{"key":"ref_35","first-page":"1633","article-title":"Mutant p53 detected in a majority of burkitt lymphoma cell lines by monoclonal antibody pab240","volume":"6","author":"Wiman","year":"1991","journal-title":"Oncogene"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"24027","DOI":"10.18632\/oncotarget.8210","article-title":"Discovery and characterization of isofistularin-3, a marine brominated alkaloid, as a new DNA demethylating agent inducing cell cycle arrest and sensitization to trail in cancer cells","volume":"7","author":"Florean","year":"2016","journal-title":"Oncotarget"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"10153","DOI":"10.1038\/ncomms10153","article-title":"Bptf is required for c-myc transcriptional activity and in vivo tumorigenesis","volume":"7","author":"Richart","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1101\/gad.585710","article-title":"The interaction between myc and miz1 is required to antagonize tgfbeta-dependent autocrine signaling during lymphoma formation and maintenance","volume":"24","author":"Muller","year":"2010","journal-title":"Genes Dev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1111\/apha.12305","article-title":"Acute response and subcellular movement of hsp27, alphab-crystallin and hsp70 in human skeletal muscle after blood-flow-restricted low-load resistance exercise","volume":"211","author":"Cumming","year":"2014","journal-title":"Acta Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2134","DOI":"10.18632\/oncotarget.3040","article-title":"DNA damage induces gdnf secretion in the tumor microenvironment with paracrine effects promoting prostate cancer treatment resistance","volume":"6","author":"Huber","year":"2015","journal-title":"Oncotarget"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"76898","DOI":"10.18632\/oncotarget.20176","article-title":"Dnmt3b overexpression contributes to aberrant DNA methylation and myc-driven tumor maintenance in t-all and burkitt\u2019s lymphoma","volume":"8","author":"Poole","year":"2017","journal-title":"Oncotarget"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/10\/11\/448\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:30:03Z","timestamp":1760196603000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/10\/11\/448"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,16]]},"references-count":41,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2018,11]]}},"alternative-id":["cancers10110448"],"URL":"https:\/\/doi.org\/10.3390\/cancers10110448","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,16]]}}}