A bacterial protease depletes c-MYC and increases survival in mouse models of bladder and colon cancer
(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.
(Less)
- author
- organization
- publishing date
- 2021-06-01
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nature Biotechnology
- volume
- 39
- issue
- 6
- pages
- 11 pages
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85100806509
- pmid:33574609
- 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
- 2024-09-19 17:02:25
@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}}, }