Results

RDF/XMLNTriplesTurtleShow queryShare ▶
SubjectPredicateObject
http://purl.uniprot.org/citations/36608459http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/36608459http://www.w3.org/2000/01/rdf-schema#comment"

Objectives

In head and neck squamous cell carcinoma (HNSCC), poor prognosis and low survival rates are associated with downregulated calprotectin. Calprotectin (S100A8/A9) inhibits cancer cell migration and invasion and facilitates G2/M cell cycle arrest. We investigated whether S100A8/A9 regulates DNA damage responses (DDR) and apoptosis in HNSCC after chemoradiation.

Materials and methods

Human HNSCC cases in TCGA were analyzed for relationships between S100A8/A9 and expression of apoptosis-related genes. Next, S100A8/A9-expressing and non-expressing carcinoma lines (two different lineages) were exposed to genotoxic agents and assessed for 53BP1 and γH2AX expression and percent of viable/dead cells. Finally, S100A8/A9-wild-type and S100A8/A9null C57BL/6j mice were treated with 4-NQO to induce oral dysplastic and carcinomatous lesions, which were compared for levels of 53BP1.

Results

In S100A8/A9-high HNSCC tumors, apoptosis-related caspase family member genes were upregulated, whereas genes limiting apoptosis were significantly downregulated based on TCGA analyses. After X-irradiation or camptothecin treatment, S100A8/A9-expressing carcinoma cells (i.e., TR146 and KB-S100A8/A9) showed significantly higher 53BP1 and γH2AX expression, DNA fragmentation, proportions of dead cells, and greater sensitivity to cisplatin than wild-type KB or TR146-S100A8/A9-KD cells. Interestingly, KB-S100A8/A9Δ113-114 cells showed similar 53BP1 and γH2AX levels to S100A8/A9-negative KB and KB-EGFP cells. After 4-NQO treatment, 53BP1 expression in oral lesions was significantly greater in calprotectin+/+ than S100A8/A9null mice.

Conclusions

In HNSCC cells, intracellular calprotectin is strongly suggested to potentiate DDR and promote apoptosis in response to genotoxic agents. Hence, patients with S100A8/A9-high HNSCC may encounter more favorable outcomes because more tumor cells enter apoptosis with increased sensitivity to chemoradiation therapy."xsd:string
http://purl.uniprot.org/citations/36608459http://purl.org/dc/terms/identifier"doi:10.1016/j.oraloncology.2022.106304"xsd:string
http://purl.uniprot.org/citations/36608459http://purl.uniprot.org/core/author"Wei Y."xsd:string
http://purl.uniprot.org/citations/36608459http://purl.uniprot.org/core/author"Herzberg M.C."xsd:string
http://purl.uniprot.org/citations/36608459http://purl.uniprot.org/core/author"Khammanivong A."xsd:string
http://purl.uniprot.org/citations/36608459http://purl.uniprot.org/core/author"Malz C."xsd:string
http://purl.uniprot.org/citations/36608459http://purl.uniprot.org/core/author"Argyris P.P."xsd:string
http://purl.uniprot.org/citations/36608459http://purl.uniprot.org/core/author"Saavedra F."xsd:string
http://purl.uniprot.org/citations/36608459http://purl.uniprot.org/core/author"Boyle W.S."xsd:string
http://purl.uniprot.org/citations/36608459http://purl.uniprot.org/core/author"Johnstone K.F."xsd:string
http://purl.uniprot.org/citations/36608459http://purl.uniprot.org/core/author"Stone I.A."xsd:string
http://purl.uniprot.org/citations/36608459http://purl.uniprot.org/core/date"2023"xsd:gYear
http://purl.uniprot.org/citations/36608459http://purl.uniprot.org/core/name"Oral Oncol"xsd:string
http://purl.uniprot.org/citations/36608459http://purl.uniprot.org/core/pages"106304"xsd:string
http://purl.uniprot.org/citations/36608459http://purl.uniprot.org/core/title"Intracellular calprotectin (S100A8/A9) facilitates DNA damage responses and promotes apoptosis in head and neck squamous cell carcinoma."xsd:string
http://purl.uniprot.org/citations/36608459http://purl.uniprot.org/core/volume"137"xsd:string
http://purl.uniprot.org/citations/36608459http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/36608459
http://purl.uniprot.org/citations/36608459http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/36608459
http://purl.uniprot.org/uniprot/#_B2R4M6-mappedCitation-36608459http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/36608459
http://purl.uniprot.org/uniprot/#_Q53X15-mappedCitation-36608459http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/36608459
http://purl.uniprot.org/uniprot/#_P05109-mappedCitation-36608459http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/36608459
http://purl.uniprot.org/uniprot/#_Q3UP42-mappedCitation-36608459http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/36608459
http://purl.uniprot.org/uniprot/#_P06702-mappedCitation-36608459http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/36608459
http://purl.uniprot.org/uniprot/#_P27005-mappedCitation-36608459http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/36608459
▶