{
  "abstract": "Undifferentiated Pleomorphic Sarcoma (UPS) is a genetically complex type of soft tissue sarcoma (STS) and there are few therapeutic options for advanced disease. Immune checkpoint blockade therapy may be of benefit to a subset of UPS patients, particularly those with elevated tumoral Programmed Cell Death Ligand 1 (PD-L1) expression and an inflamed tumour microenvironment. From transcriptomic analyses we previously identified Signal Transducer and Activator of Transcription 1 (STAT1) expression, a key mediator of interferon-γ (IFN-γ) signaling, as enriched in a cohort of UPS cases with elevated PD-L1 levels that were observed to have an improved clinical outcome. This led us to investigate the role of STAT1 in UPS biology. We examined the effects of STAT1 loss, and overexpression of either wild type or tyrosine phosphorylation-deficient STAT1 in primary human UPS cell lines. We observed that IFN-γ treatment decreased cell counts, increased cell death, and induced the secretion of CXCR3 ligands in a STAT1-dependent manner. Overexpression of wild type STAT1, but not a tyrosine to phenylalanine phospho-mutant (Y701F), restored IFN-γ-mediated cell death and cytokine secretion, highlighting the importance of Y701 phosphorylation in STAT1-associated antitumour functions. STAT1 Y701 phosphorylation status was associated with gene expression changes that were cell line specific. Together, these findings shed light on the central role of STAT1, and specifically the Y701 phosphorylation, in mediating IFN-γ signaling and related phenotypes. This study underscores the need for further exploration of the role of STAT1 phosphorylation in tumor-immune interactions within UPS.",
  "abstract_shown": true,
  "affiliations": [
    "Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada.",
    "Department of Molecular Genetics, University of Toronto, Toronto, Canada.",
    "Department of Surgical Oncology, Princess Margaret Cancer Centre/Mount Sinai Hospital, Toronto, Canada.",
    "Department of Surgery, Mount Sinai Hospital, Sinai Health, Toronto, Canada.",
    "University of Toronto Musculoskeletal Oncology Unit, Division of Orthopaedic Surgery, Toronto, Canada.",
    "Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.",
    "Institute of Medical Science, University of Toronto, Toronto, Canada."
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Victoria S Coward",
      "orcid": "0009-0008-0569-7691"
    },
    {
      "affs": [
        0
      ],
      "name": "Nalan Gokgoz"
    },
    {
      "affs": [
        0,
        2,
        3,
        4,
        5
      ],
      "name": "Kim M Tsoi"
    },
    {
      "affs": [
        0,
        2,
        3,
        4,
        5,
        6
      ],
      "name": "Jay S Wunder"
    },
    {
      "affs": [
        0,
        1,
        5
      ],
      "name": "Irene L Andrulis"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/a99bs8m518px2.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pone.0361295",
  "fulltext_url": "https://europepmc.org/articles/PMC13704806",
  "id": "a99bs8m518px2",
  "issns": [
    "1932-6203"
  ],
  "landing_url": "https://doi.org/10.1371/journal.pone.0361295",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2730|Cytokine Signaling Pathways and Interactions"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteins/Post-translational modification/Phosphorylation"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cell processes/Cell death"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Signal transduction/Cell signaling/STAT signaling"
    ],
    [
      "plos",
      "/Biology and life sciences/Developmental biology/Molecular development/Cytokines"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Gene expression"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Gene expression/Gene regulation"
    ],
    [
      "plos",
      "/Biology and life sciences/Immunology/Immune system/Innate immune system/Cytokines"
    ],
    [
      "plos",
      "/Biology and life sciences/Physiology/Immune physiology/Cytokines"
    ],
    [
      "plos",
      "/Biology and life sciences/Physiology/Physiological processes/Secretion"
    ],
    [
      "plos",
      "/Medicine and health sciences/Immunology/Immune system/Innate immune system/Cytokines"
    ],
    [
      "plos",
      "/Research and analysis methods/Cell enumeration techniques"
    ]
  ],
  "openalex": "W7223663167",
  "pdf_url": "https://europepmc.org/articles/PMC13704806?pdf=render",
  "pmcid": "PMC13704806",
  "pmid": "42932326",
  "published": "2026-10-26",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/a99bs8m518px2.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:17Z",
      "native_id": "10.1371/journal.pone.0361295",
      "source": "plos",
      "url": "https://doi.org/10.1371/journal.pone.0361295"
    },
    {
      "first_seen": "2026-10-30T12:21:51Z",
      "native_id": "MED:42932326",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42932326"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "plos:gene expression",
      "subfield": "molecular-biology"
    },
    {
      "field": "biology",
      "origin": "plos:cell biology",
      "subfield": "cell-biology"
    },
    {
      "field": "biology",
      "origin": "plos:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "The effect of STAT1 expression and the Y701 phosphorylation on primary Undifferentiated Pleomorphic Sarcoma cells",
  "title_text": "The effect of STAT1 expression and the Y701 phosphorylation on primary Undifferentiated Pleomorphic Sarcoma cells",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:51Z",
  "url": "https://research.draconitic.com/paper/a99bs8m518px2",
  "venue": "PLOS One",
  "versions": []
}