{
  "abstract": "Oncogenic Ras signaling drives cell growth and tumor progression through acquired changes in gene expression that promote the malignant phenotype. One such gene, SERPINE1, which encodes plasminogen activator inhibitor-1 (PAI-1), is a poor prognostic biomarker in human cancers and a p53 target gene. This study utilizes v-KRAS-transformed renal epithelial (KNRK) cells to define how PAI-1 overexpression influences cell morphology, growth dynamics, and migratory behavior. KNRK cells were engineered to express PAI-1 using a CMV-driven lentiviral expression vector, with a CMV drug resistance only vector as a control, followed by stable selection with puromycin. Cellular morphology and growth characteristics were assessed by microscopic imaging and cell density analysis; cell migration was evaluated using a scratch-wound assay. Western blotting and immunofluorescence served to assess expression and subcellular localization of PAI-1, p21, and p53 in CMV-control and PAI-1 cells. CMV-PAI-1 cells exhibited a shift to a mesenchymal, more pleomorphic and motile phenotype, with increased spreading, irregular borders and decreased cell–cell adhesion. Wound closure in CMV-PAI-1 cells was significantly increased compared to CMV-control cells (p < 0.001), indicating enhanced migratory capacity, with prominent deposition of PAI-1 into cellular migration trails. CMV-PAI-1 cells had a reduced growth rate, an approximately 4-fold increase in p-p53 and a shift in p21 from a perinuclear localization in controls to predominantly cytoplasmic in CMV-PAI-1 cells. These findings highlight PAI-1 as a potential driver of mesenchymal cell traits in KRAS-transformed renal epithelial cells.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Regenerative & Cancer Cell Biology, Albany Medical College, Albany, NY 12208, USA"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Naziba Nuha",
      "orcid": "0009-0004-3158-9679"
    },
    {
      "affs": [
        0
      ],
      "name": "Craig E. Higgins"
    },
    {
      "affs": [
        0
      ],
      "name": "Stephen P. Higgins"
    },
    {
      "affs": [
        0
      ],
      "name": "Rohan Samarakoon",
      "orcid": "0000-0003-0890-4947"
    },
    {
      "affs": [
        0
      ],
      "name": "Paul J. Higgins",
      "orcid": "0000-0001-5208-1197"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3z805c673d2fw.bib",
  "cited_by": 0,
  "doi": "10.3390/biom16101517",
  "fulltext_url": null,
  "id": "3z805c673d2fw",
  "issns": [
    "2218-273X"
  ],
  "landing_url": "https://www.mdpi.com/2218-273X/16/10/1517",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1306|Protease and Inhibitor Mechanisms"
    ]
  ],
  "openalex": "W7222954726",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-19",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/3z805c673d2fw.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:59Z",
      "native_id": "10.3390/biom16101517",
      "source": "crossref",
      "url": "https://www.mdpi.com/2218-273X/16/10/1517"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:1306|Protease and Inhibitor Mechanisms",
      "subfield": "oncology"
    }
  ],
  "title": "Engineered SERPINE1 Overexpression Activates the pp53/p21 Pathway and Promotes a Growth-Restricted, Migratory Phenotype in KRAS-Transformed Renal Proximal Tubular Cells",
  "title_text": "Engineered SERPINE1 Overexpression Activates the pp53/p21 Pathway and Promotes a Growth-Restricted, Migratory Phenotype in KRAS-Transformed Renal Proximal Tubular Cells",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:59Z",
  "url": "https://research.draconitic.com/paper/3z805c673d2fw",
  "venue": "Biomolecules",
  "versions": []
}