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Πέμπτη 15 Νοεμβρίου 2018

Cancers, Vol. 10, Pages 448: Targeting the MYC Oncogene in Burkitt Lymphoma through HSP90 Inhibition

Cancers, Vol. 10, Pages 448: Targeting the MYC Oncogene in Burkitt Lymphoma through HSP90 Inhibition

Cancers doi: 10.3390/cancers10110448

Authors: Candace J. Poole Wenli Zheng Haesung Lee Danielle Young Atul Lodh Ahmed Chadli Jan van Riggelen

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.



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