<?xml version='1.0' encoding='UTF-8'?>
<ProteomeXchangeDataset id="PXD031676" formatVersion="1.4.0" xsi:noNamespaceSchemaLocation="proteomeXchange-1.4.0.xsd" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance">
  <CvList>
    <Cv id="MS" fullName="PSI-MS" uri="https://raw.githubusercontent.com/HUPO-PSI/psi-ms-Cv/master/psi-ms.obo"/>
    <Cv id="MOD" fullName="PSI-MOD" uri="https://raw.githubusercontent.com/HUPO-PSI/psi-mod-CV/master/PSI-MOD.obo"/>
    <Cv id="UNIMOD" fullName="UNIMOD" uri="http://www.unimod.org/obo/unimod.obo"/>
  </CvList>
  <ChangeLog>
    <ChangeLogEntry>Added PubMed Id</ChangeLogEntry>
  </ChangeLog>
  <DatasetSummary announceDate="2022-05-17" hostingRepository="PanoramaPublic" 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.</Description>
    <ReviewLevel>
      <cvParam cvRef="MS" accession="MS:1002854" name="Peer-reviewed dataset"/>
    </ReviewLevel>
    <RepositorySupport>
      <cvParam cvRef="MS" accession="MS:1002856" name="Supported dataset by repository"/>
    </RepositorySupport>
  </DatasetSummary>
  <DatasetIdentifierList>
    <DatasetIdentifier>
      <cvParam cvRef="MS" accession="MS:1001919" name="ProteomeXchange accession number" value="PXD031676"/>
      <cvParam cvRef="MS" accession="MS:1001921" name="ProteomeXchange accession number version number" value="4"/>
    </DatasetIdentifier>
    <DatasetIdentifier>
      <cvParam cvRef="MS" accession="MS:1002872" name="Panorama Public dataset identifier" value="https://panoramaweb.org/StaphylococcalPSM.url"/>
    </DatasetIdentifier>
  </DatasetIdentifierList>
  <DatasetOriginList>
    <DatasetOrigin>
      <cvParam cvRef="MS" accession="MS:1002868" name="Original data"/>
    </DatasetOrigin>
  </DatasetOriginList>
  <SpeciesList>
    <Species>
      <cvParam cvRef="MS" accession="MS:1001469" name="taxonomy: scientific name" value="Staphylococcus epidermidis"/>
      <cvParam cvRef="MS" accession="MS:1001467" name="taxonomy: NCBI TaxID" value="1282"/>
    </Species>
    <Species>
      <cvParam cvRef="MS" accession="MS:1001469" name="taxonomy: scientific name" value="Staphylococcus aureus"/>
      <cvParam cvRef="MS" accession="MS:1001467" name="taxonomy: NCBI TaxID" value="1280"/>
    </Species>
    <Species>
      <cvParam cvRef="MS" accession="MS:1001469" name="taxonomy: scientific name" value="Staphylococcus"/>
      <cvParam cvRef="MS" accession="MS:1001467" name="taxonomy: NCBI TaxID" value="1279"/>
    </Species>
    <Species>
      <cvParam cvRef="MS" accession="MS:1001469" name="taxonomy: scientific name" value="Staphylococcus capitis"/>
      <cvParam cvRef="MS" accession="MS:1001467" name="taxonomy: NCBI TaxID" value="29388"/>
    </Species>
  </SpeciesList>
  <InstrumentList>
    <Instrument id="instrument_1">
      <cvParam cvRef="MS" accession="MS:1000935" name="6470A Triple Quadrupole LC/MS"/>
    </Instrument>
  </InstrumentList>
  <ModificationList>
    <cvParam cvRef="UNIMOD" accession="UNIMOD:122" name="Formyl"/>
  </ModificationList>
  <ContactList>
    <Contact id="lab_head">
      <cvParam cvRef="MS" accession="MS:1002332" name="lab head"/>
      <cvParam cvRef="MS" accession="MS:1000586" name="contact name" value="Michelle Hill"/>
      <cvParam cvRef="MS" accession="MS:1000589" name="contact email" value="michelle.hill@qimrberghofer.edu.au"/>
      <cvParam cvRef="MS" accession="MS:1000590" name="contact affiliation" value="QIMR Berghofer Medical Research Institute,  Precision &amp; Systems Biomedicine, Herston, Brisbane, Queensland, Australia"/>
    </Contact>
    <Contact id="dataset_submitter">
      <cvParam cvRef="MS" accession="MS:1002037" name="dataset submitter"/>
      <cvParam cvRef="MS" accession="MS:1000586" name="contact name" value="Thomas Stoll"/>
      <cvParam cvRef="MS" accession="MS:1000589" name="contact email" value="thomas.stoll@qimrberghofer.edu.au"/>
      <cvParam cvRef="MS" accession="MS:1000590" name="contact affiliation" value="QIMR Berghofer Medical Research Institute,  Precision &amp; Systems Biomedicine, Herston, Brisbane, Queensland, Australia"/>
    </Contact>
  </ContactList>
  <PublicationList>
    <Publication id="PMID35565272">
      <cvParam cvRef="MS" accession="MS:1000879" name="PubMed identifier" value="35565272"/>
      <cvParam cvRef="MS" accession="MS:1002866" name="Reference" value="Krueger A, Mohamed A, Kolka CM, Stoll T, Zaugg J, Linedale R, Morrison M, Soyer HP, Hugenholtz P, Frazer IH, Hill MM. Skin Cancer-Associated &lt;i>S. aureus&lt;/i> Strains Can Induce DNA Damage in Human Keratinocytes by Downregulating DNA Repair and Promoting Oxidative Stress. Cancers (Basel). 2022 Apr 25;14(9):2143. doi: 10.3390/cancers14092143. PMID: 35565272."/>
    </Publication>
  </PublicationList>
  <KeywordList>
    <cvParam cvRef="MS" accession="MS:1001925" name="submitter keyword" value="Skin"/>
    <cvParam cvRef="MS" accession="MS:1001925" name="submitter keyword" value="S. aureus secretome"/>
    <cvParam cvRef="MS" accession="MS:1001925" name="submitter keyword" value="multiomics"/>
    <cvParam cvRef="MS" accession="MS:1001925" name="submitter keyword" value="actinic keratosis"/>
    <cvParam cvRef="MS" accession="MS:1001925" name="submitter keyword" value="squamous cell carcinoma"/>
    <cvParam cvRef="MS" accession="MS:1001925" name="submitter keyword" value="DNA damage"/>
  </KeywordList>
  <FullDatasetLinkList>
    <FullDatasetLink>
      <cvParam cvRef="MS" accession="MS:1002873" name="Panorama Public dataset URI" value="https://panoramaweb.org/StaphylococcalPSM.url"/>
    </FullDatasetLink>
  </FullDatasetLinkList>
</ProteomeXchangeDataset>