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

Butler, Daniel S.C. LU ; Cafaro, Caterina LU ; Putze, Johannes ; Wan, Murphy Lam Yim LU ; Tran, Thi Hien LU ; Ambite, Ines LU orcid ; Ahmadi, Shahram LU ; Kjellström, Sven LU ; Welinder, Charlotte LU and Chao, Sing Ming , et al. (2021) In Nature Biotechnology 39(6). p.754-764
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Biotechnology
volume
39
issue
6
pages
11 pages
publisher
Nature Publishing Group
external identifiers
  • pmid:33574609
  • scopus:85100806509
ISSN
1087-0156
DOI
10.1038/s41587-020-00805-3
language
English
LU publication?
yes
id
6a05db2c-2e4a-404a-8e5d-ecef82f55007
date added to LUP
2021-03-03 08:26:31
date last changed
2022-06-29 03:03:15
@article{6a05db2c-2e4a-404a-8e5d-ecef82f55007,
  abstract     = {{<p>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.</p>}},
  author       = {{Butler, Daniel S.C. and Cafaro, Caterina and Putze, Johannes and Wan, Murphy Lam Yim and Tran, Thi Hien and Ambite, Ines and Ahmadi, Shahram and Kjellström, Sven and Welinder, Charlotte and Chao, Sing Ming and Dobrindt, Ulrich and Svanborg, Catharina}},
  issn         = {{1087-0156}},
  language     = {{eng}},
  month        = {{06}},
  number       = {{6}},
  pages        = {{754--764}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Biotechnology}},
  title        = {{A bacterial protease depletes c-MYC and increases survival in mouse models of bladder and colon cancer}},
  url          = {{http://dx.doi.org/10.1038/s41587-020-00805-3}},
  doi          = {{10.1038/s41587-020-00805-3}},
  volume       = {{39}},
  year         = {{2021}},
}