A bacterial protease depletes c-MYC and increases survival in mouse models of bladder and colon cancer

Daniel S.C. Butler, Caterina Cafaro, Johannes Putze, Murphy Lam Yim Wan, Thi Hien Tran, Ines Ambite, Shahram Ahmadi, Sven Kjellström, Charlotte Welinder, Sing Ming Chao, Ulrich Dobrindt, Catharina Svanborg

Research output: Contribution to journalArticlepeer-review

15 Citations (SciVal)

Abstract

Is the oncogene MYC upregulated or hyperactive? In the majority of human cancers, finding agents that target c-MYC has proved difficult. Here we report specific bacterial effector molecules that inhibit cellular MYC (c-MYC) in human cells. We show that uropathogenic Escherichia coli (UPEC) degrade the c-MYC protein and attenuate MYC expression in both human cells and animal tissues. c-MYC protein was rapidly degraded by both cell-free bacterial lysates and the purified bacterial protease Lon. In mice, intravesical or peroral delivery of Lon protease delayed tumor progression and increased survival in MYC-dependent bladder and colon cancer models, respectively. These results suggest that bacteria have evolved strategies to control c-MYC tissue levels in the host and that the Lon protease shows promise for therapeutic targeting of c-MYC in cancer.

Original languageEnglish
Pages (from-to)754–764
Number of pages11
JournalNature Biotechnology
Volume39
Issue number6
Early online date2021 Feb 11
DOIs
Publication statusPublished - 2021 Jun 1

Subject classification (UKÄ)

  • Microbiology in the medical area

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