{
  "abstract": "Background/Objectives: Glutathione S-transferase theta 2 (GSTT2) is highly expressed in esophageal tissues from African American (AA) compared with European American (EA) individuals, but its localization, regulation, and relevance to esophageal adenocarcinoma progression remain unclear. Methods: Here, we combined FISH, immunofluorescence, patient-derived culture models, cell-cycle synchronization, biochemical perturbation, and transcriptomics to define GSTT2 expression in normal and neoplastic esophageal contexts. Results: In developing and adult esophageal tissues, GSTT2 mRNA and protein were broadly distributed across squamous epithelium and lamina propria, co-localizing with p63-positive basal/progenitor cells and extending into differentiated compartments, with no major ancestry-associated differences in spatial patterning. In Barrett's esophagus, GSTT2 protein was retained in metaplastic columnar epithelium and slightly elevated in dysplastic versus adjacent non-dysplastic regions. GSTT2 mRNA was highest in normal squamous esophagus, reduced during Barrett's-to-adenocarcinoma progression, but increased in treatment-resistant esophageal adenocarcinoma (EAC). In resistant EAC, GSTT2 co-expression shifted from homeostatic antioxidant programs to proliferation and mitotic pathways, including the G2-M checkpoint, E2F targets, and Reactome Cell Cycle, with leading-edge regulators CDK1 and CDC20. Sequence analysis identified putative APC-C and FBXW7 recognition motifs. In synchronized cells, GSTT2 abundance declined during S-G2/M and increased during mitotic exit/early G1 in cytosolic and membrane fractions. Forskolin, a dual inhibitor of FBXW7 and CDC20, stabilized GSTT2 and rescued CDC20- or FBXW7-associated loss, implicating APC-CDC20 and FBXW7 pathways in GSTT2 turnover. In EAC cells, by contrast, CDC20 was found to be a cooperative partner stabilizing GSTT2. Conclusions: These findings identify GSTT2 as a spatially widespread, ancestry-associated, cell-cycle-regulated protein with potential oncogenic roles in EAC resistance.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Medicine, Division of Gastroenterology & Hepatology, University of Colorado Cancer Center, Anschutz Medical Campus, Aurora, CO 80045, USA.",
    "Katy O. and Paul M. Rady Esophageal and Gastric Center of Excellence, University of Colorado Cancer Center, Anschutz Medical Campus, Aurora, CO 80045, USA.",
    "Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, USA.",
    "Department of Gastroenterology, University of Michigan, Ann Arbor, MI 48109, USA.",
    "Department of Oncology, University of Colorado Cancer Center, Anschutz Medical Campus, Aurora, CO 80045, USA.",
    "Department of Surgery, University of Colorado Cancer Center, Anschutz Medical Campus, Aurora, CO 80045, USA.",
    "Department of Surgery, University of Michigan, Ann Arbor, MI 48109, USA."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 18,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Daysha Ferrer-Torres",
      "orcid": "0000-0002-3576-0347"
    },
    {
      "affs": [
        2
      ],
      "name": "Paramita Ray"
    },
    {
      "affs": [
        0
      ],
      "name": "Noah Etzioni",
      "orcid": "0009-0000-7487-1552"
    },
    {
      "affs": [
        3
      ],
      "name": "Max A Hammer"
    },
    {
      "affs": [
        2
      ],
      "name": "Archismaan Ghosh",
      "orcid": "0000-0001-8756-2820"
    },
    {
      "affs": [
        2
      ],
      "name": "Meilan Liu"
    },
    {
      "affs": [
        2
      ],
      "name": "Vinay Jeeyar",
      "orcid": "0000-0002-3662-8815"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Sachin Wani"
    },
    {
      "affs": [
        1,
        4
      ],
      "name": "Sunnie S Kim",
      "orcid": "0009-0008-3871-5112"
    },
    {
      "affs": [
        1,
        5
      ],
      "name": "Benedetto Mungo",
      "orcid": "0000-0002-1319-7653"
    },
    {
      "affs": [
        1,
        5
      ],
      "name": "Stefan Marasligiller"
    },
    {
      "affs": [
        3
      ],
      "name": "Danielle Kim Turgeon",
      "orcid": "0000-0003-1010-819X"
    },
    {
      "affs": [
        6
      ],
      "name": "Jules Lin",
      "orcid": "0000-0003-4733-0659"
    },
    {
      "affs": [
        6
      ],
      "name": "Peter D R Higgins"
    },
    {
      "affs": [
        3
      ],
      "name": "Jason R Spence"
    },
    {
      "affs": [
        6
      ],
      "name": "Kiran H Lagisetty"
    },
    {
      "affs": [
        6
      ],
      "name": "David G Beer"
    },
    {
      "affs": [
        2
      ],
      "name": "Dipankar Ray",
      "orcid": "0000-0002-1297-2312"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/b3gywqbard3x3.bib",
  "cited_by": 0,
  "doi": "10.3390/cancers18193220",
  "fulltext_url": "https://europepmc.org/articles/PMC13664410",
  "id": "b3gywqbard3x3",
  "issns": [
    "2072-6694"
  ],
  "landing_url": "https://europepmc.org/article/MED/42882914",
  "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",
      "1312|Glutathione Transferases and Polymorphisms"
    ]
  ],
  "openalex": "W7220666612",
  "pdf_url": "https://europepmc.org/articles/PMC13664410?pdf=render",
  "pmcid": "PMC13664410",
  "pmid": "42882914",
  "published": "2026-10-06",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/b3gywqbard3x3.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:00Z",
      "native_id": "MED:42882914",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42882914"
    },
    {
      "first_seen": "2026-10-30T12:19:58Z",
      "native_id": "10.3390/cancers18193220",
      "source": "crossref",
      "url": "https://www.mdpi.com/2072-6694/18/19/3220"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Glutathione Transferases and Polymorphisms",
      "subfield": "molecular-biology"
    }
  ],
  "title": "GSTT2 Switches from a Homeostatic Antioxidant to a Cell-Cycle-Coupled Factor in Therapy-Resistant Esophageal Adenocarcinoma.",
  "title_text": "GSTT2 Switches from a Homeostatic Antioxidant to a Cell-Cycle-Coupled Factor in Therapy-Resistant Esophageal Adenocarcinoma.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:58Z",
  "url": "https://research.draconitic.com/paper/b3gywqbard3x3",
  "venue": "Cancers",
  "versions": []
}