PXD031676

PXD031676 is an original dataset announced via ProteomeXchange.

Title	Skin cancer-associated S. aureus downregulates DNA repair mechanisms, and promotes oxidative stress and DNA damage in human keratinocytes
Description	Actinic keratoses (AK) are premalignant lesions common on photo-damaged skin that, over time, can progress to squamous cell carcinoma (SCC). A high bacterial load of Staphylococcus aureus is associated with AK and SCC but it is unknown whether this has a direct impact on skin cancer development. To determine whether S. aureus is able to trigger pro-tumorigenic skin responses, we performed RNAseq and shotgun proteomics on primary human keratinocytes after challenge with sterile culture supernatant (‘secretome’) from S. aureus clinical strains isolated from AK and SCC. Certain S. aureus secretomes induced keratinocytes to overexpress SCC biomarkers that have been associated with skin carcinogenesis, and upregulate the expression of enzymes linked with reduced skin barrier function. Further, S. aureus secretomes downregulated DNA repair mechanisms and induced oxidative stress markers. Subsequent experiments confirmed that exposure to SCC-derived S. aureus secretomes lead to increased intracellular ROS levels and DNA damage in primary human keratinocytes. Altogether, this study reveal a novel mechanism for the pro-tumorigenic activity of S. aureus. Further studies are required to determine whether S. aureus products promote SCC development in vivo, which would have important implications for the treatment of AK and prevention of SCC.
HostingRepository	PanoramaPublic
AnnounceDate	2022-05-17
AnnouncementXML	Submission_2022-05-17_16:22:16.377.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Thomas Stoll
SpeciesList	scientific name: Staphylococcus epidermidis; NCBI TaxID: 1282; scientific name: Staphylococcus aureus; NCBI TaxID: 1280; scientific name: Staphylococcus; NCBI TaxID: 1279; scientific name: Staphylococcus capitis; NCBI TaxID: 29388;
ModificationList	Formyl
Instrument	6470A Triple Quadrupole LC/MS

Revision	Datetime	Status	ChangeLog Entry
0	2022-02-14 22:13:29	ID requested
1	2022-04-19 07:36:40	announced
2	2022-04-27 06:30:30	announced	: Added publication
3	2022-04-27 06:36:59	announced	: Updated citation
⏵ 4	2022-05-17 16:22:18	announced	: Added PubMed Id

Krueger A, Mohamed A, Kolka CM, Stoll T, Zaugg J, Linedale R, Morrison M, Soyer HP, Hugenholtz P, Frazer IH, Hill MM, Strains Can Induce DNA Damage in Human Keratinocytes by Downregulating DNA Repair and Promoting Oxidative Stress. Cancers (Basel), 14(9):(2022) [pubmed]

submitter keyword: Skin, S. aureus secretome, multiomics, actinic keratosis, squamous cell carcinoma, DNA damage

Michelle Hill
contact affiliation	QIMR Berghofer Medical Research Institute, Precision & Systems Biomedicine, Herston, Brisbane, Queensland, Australia
contact email	michelle.hill@qimrberghofer.edu.au
lab head
Thomas Stoll
contact affiliation	QIMR Berghofer Medical Research Institute, Precision & Systems Biomedicine, Herston, Brisbane, Queensland, Australia
contact email	thomas.stoll@qimrberghofer.edu.au
dataset submitter

Panorama Public dataset URI