Targeting the MYC oncogene in burkitt lymphoma through HSP90 inhibition

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

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number448
JournalCancers
Volume10
Issue number11
DOIs
StatePublished - Nov 16 2018

Fingerprint

Burkitt Lymphoma
Oncogenes
17-(dimethylaminoethylamino)-17-demethoxygeldanamycin
tanespimycin
Proteins
Proteasome Inhibitors
Proteasome Endopeptidase Complex
Immunoprecipitation
Neoplasms
Down-Regulation
Cell Proliferation
Cell Line
Genes

Keywords

  • 17-AAG
  • 17-DMAG
  • Burkitt lymphoma
  • HSP90
  • MYC

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Poole, C. J., Zheng, W., Lee, H., Young, D., Lodh, A., Chadli, A., & van Riggelen, J. (2018). Targeting the MYC oncogene in burkitt lymphoma through HSP90 inhibition. Cancers, 10(11), [448]. https://doi.org/10.3390/cancers10110448

Targeting the MYC oncogene in burkitt lymphoma through HSP90 inhibition. / Poole, Candace J.; Zheng, Wenli; Lee, Haesung; Young, Danielle; Lodh, Atul; Chadli, Ahmed; van Riggelen, Jan.

In: Cancers, Vol. 10, No. 11, 448, 16.11.2018.

Research output: Contribution to journalArticle

Poole, CJ, Zheng, W, Lee, H, Young, D, Lodh, A, Chadli, A & van Riggelen, J 2018, 'Targeting the MYC oncogene in burkitt lymphoma through HSP90 inhibition', Cancers, vol. 10, no. 11, 448. https://doi.org/10.3390/cancers10110448
Poole, Candace J. ; Zheng, Wenli ; Lee, Haesung ; Young, Danielle ; Lodh, Atul ; Chadli, Ahmed ; van Riggelen, Jan. / Targeting the MYC oncogene in burkitt lymphoma through HSP90 inhibition. In: Cancers. 2018 ; Vol. 10, No. 11.
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