umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Infection with genotoxin-producing Salmonella enterica synergises with loss of the tumour suppressor APC in promoting genomic instability via the PI3K pathway in colonic epithelial cells
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
Show others and affiliations
2019 (English)In: Cellular Microbiology, ISSN 1462-5814, E-ISSN 1462-5822, Vol. 21, no 12, article id e13099Article in journal (Refereed) Published
Abstract [en]

Several commensal and pathogenic Gram-negative bacteria produce DNA-damaging toxins that are considered bona fide carcinogenic agents. The microbiota of colorectal cancer (CRC) patients is enriched in genotoxin-producing bacteria, but their role in the pathogenesis of CRC is poorly understood. The adenomatous polyposis coli (APC) gene is mutated in familial adenomatous polyposis and in the majority of sporadic CRCs. We investigated whether the loss of APC alters the response of colonic epithelial cells to infection by Salmonella enterica, the only genotoxin-producing bacterium associated with cancer in humans. Using 2D and organotypic 3D cultures, we found that APC deficiency was associated with sustained activation of the DNA damage response, reduced capacity to repair different types of damage, including DNA breaks and oxidative damage, and failure to induce cell cycle arrest. The reduced DNA repair capacity and inability to activate adequate checkpoint responses was associated with increased genomic instability in APC-deficient cells exposed to the genotoxic bacterium. Inhibition of the checkpoint response was dependent on activation of the phosphatidylinositol 3-kinase pathway. These findings highlight the synergistic effect of the loss of APC and infection with genotoxin-producing bacteria in promoting a microenvironment conducive to malignant transformation.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019. Vol. 21, no 12, article id e13099
Keywords [en]
APC, bacteria and cancer, bacterial genotoxin, DNA damage response, DNA repair, organotypic del, tumour-suppressor gene
National Category
Microbiology
Identifiers
URN: urn:nbn:se:umu:diva-167179DOI: 10.1111/cmi.13099ISI: 000482652700001PubMedID: 31414579Scopus ID: 2-s2.0-85071087704OAI: oai:DiVA.org:umu-167179DiVA, id: diva2:1384665
Available from: 2020-01-10 Created: 2020-01-10 Last updated: 2020-01-10Bibliographically approved

Open Access in DiVA

fulltext(764 kB)10 downloads
File information
File name FULLTEXT01.pdfFile size 764 kBChecksum SHA-512
4be3a72bcd446fa72d4bda568f87b70db014166e8f9bab8f1dadbe63a9de54996c72e6153380ef66dcf529eb5ac5890fb504686196c51bb3360e08e7bb26d6da
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMedScopus

Authority records BETA

Bergonzini, AnnaFrisan, Teresa

Search in DiVA

By author/editor
Martin, Oceane C. B.Bergonzini, AnnaFrisan, Teresa
By organisation
Department of Molecular Biology (Faculty of Medicine)Department of Molecular Biology (Faculty of Science and Technology)
In the same journal
Cellular Microbiology
Microbiology

Search outside of DiVA

GoogleGoogle Scholar
Total: 10 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 22 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf