{
  "abstract": "Skin cutaneous melanoma (SKCM) is a highly metastatic and invasive malignancy. Keratin 5 (KRT5) and serine protease inhibitor B5 (SERPINB5/Maspin) have been reported to play crucial roles in various cancers; however, their interaction and the underlying molecular mechanisms in melanoma remain unclear. This study aimed to investigate the functional roles of KRT5 and SERPINB5 in melanoma progression and elucidate the mechanisms underlying their synergistic effects. Protein-protein interaction (PPI) network analysis of differentially expressed genes (DEGs) in SKCM was performed using the STRING database. Hub genes were identified via Cytoscape, and their interactions and colocalization were validated by immunofluorescence (IF) and co-immunoprecipitation (Co-IP). In A375 cells, the effects of KRT5 and SERPINB5 on cellular phenotypes were evaluated via overexpression (oe-KRT5, oe-SERPINB5) and p53 knockdown (sh-p53). Functional assays-including wound healing, Transwell, cell-matrix adhesion, 5-ethynyl-2'-deoxyuridine (EdU) incorporation, and flow cytometry-were employed to assess cell cycle distribution and apoptosis. Changes in key p53 signaling pathways and downstream molecules were detected via Western Blot and quantitative real-time polymerase chain reaction (RT-qPCR). PPI network analysis identified KRT5 and SERPINB5 as key hub genes. IF and Co-IP experiments confirmed their direct molecular interaction in A375 cells. Functionally, KRT5/SERPINB5 co-expression synergistically inhibited cell migration, invasion, cell-matrix adhesion, and proliferation while inducing G1 cell cycle arrest and apoptosis. Mechanistically, their co-expression specifically activated the p53 signaling pathway; p53 knockdown reversed the functional phenotypes induced by KRT5/SERPINB5 co-expression. Further mechanistic studies revealed that KRT5/SERPINB5 downregulated the cell cycle-related genes cyclin A2 (CCNA2) and cyclin-dependent kinase 1 (CDK1) and upregulated the expression of cell adhesion molecule E-cadherin (CDH1) through p53 activation. KRT5 and SERPINB5 synergistically activate the p53 pathway, modulate downstream gene networks involved in cell cycle and adhesion, and thereby exert cooperative tumor-suppressive effects by inhibiting cell-matrix adhesion, migration, and invasion, as well as inducing cell cycle arrest.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Anorectal Surgery, The First Affiliated Hospital of Lishui University, Lishui, China.",
    "Department of Anorectal Surgery, Lishui People's Hospital, Lishui, China.",
    "Department of Dermatology and Venereology, Suichang County People's Hospital (New Campus), Lishui, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Bi-Shun Yi",
      "orcid": "0009-0003-7069-8045"
    },
    {
      "affs": [
        2
      ],
      "name": "Yan-Shan Fan",
      "orcid": "0009-0008-8838-4067"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/62t8e8fysm77h.bib",
  "cited_by": 0,
  "doi": "10.21037/tcr-2026-0866",
  "fulltext_url": "https://europepmc.org/articles/PMC13743198",
  "id": "62t8e8fysm77h",
  "issns": [
    "2218-676X",
    "2219-6803"
  ],
  "landing_url": "https://europepmc.org/article/MED/42997892",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Melanoma and MAPK Pathways"
    ]
  ],
  "openalex": "W7224111206",
  "pdf_url": "https://europepmc.org/articles/PMC13743198?pdf=render",
  "pmcid": "PMC13743198",
  "pmid": "42997892",
  "published": "2026-10-23",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/62t8e8fysm77h.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T15:20:34Z",
      "native_id": "MED:42997892",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42997892"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Melanoma and MAPK Pathways",
      "subfield": "molecular-biology"
    }
  ],
  "title": "KRT5 and SERPINB5 cooperatively regulate the p53 pathway to inhibit cell adhesion and cell cycle abnormalities, suppressing skin melanoma progression.",
  "title_text": "KRT5 and SERPINB5 cooperatively regulate the p53 pathway to inhibit cell adhesion and cell cycle abnormalities, suppressing skin melanoma progression.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-10T03:20:49Z",
  "url": "https://research.draconitic.com/paper/62t8e8fysm77h",
  "venue": "Translational cancer research",
  "versions": []
}