{
  "abstract": "p21-Activated kinase 4 (PAK4) is widely dysregulated and acts as an oncogene in multiple cancers, and the inhibition or knockout of PAK4 has shown excellent therapeutic effects in inhibiting tumor progression in combination with immunotherapy across a variety of cancers. Previously, we reported our self-developed peptide proteolysis-targeting chimera (PROTAC) drug PpD, which specifically and selectively degrades the PAK4 protein to effectively inhibit the growth of renal cancer tumors. In this study, we confirmed that the PAK4 protein is highly expressed in bladder cancer (BLCA) tissues. Moreover, we established PAK4 knockout BLCA cell lines and explored the regulatory mechanisms of PAK4 in BLCA via RNA sequencing. Our RNA sequencing results revealed that PAK4 promotes the cell cycle progression of BLCA cells and inhibits apoptosis. Comparative studies of the PAK4 knockout cell lines T-24 sg/PAK4 and 5637 sg/PAK4 with PpD drug treatment revealed that both PAK4 knockout and PpD drug treatment inhibited the ERK1/2/CDK4 pathway, thereby blocking the cell cycle transition from the G1 phase to the S phase, and both induced caspase-3-mediated apoptotic cell death. In vivo animal experiments also confirmed that the growth of BLCA cells was significantly inhibited in both the PAK4 knockout group and the PpD drug-treated group. Collectively, our findings indicate that PpD exhibits potent anti-tumor activity against BLCA and holds promising potential for therapeutic application in other cancers.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Urology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China",
    "Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Shan Xu"
    },
    {
      "affs": [
        1
      ],
      "name": "Hongjun Xie"
    },
    {
      "name": "Zhao Yang"
    },
    {
      "name": "Zhenkun Ma"
    },
    {
      "name": "Xiaojing Bai"
    },
    {
      "name": "Xiaoyu Feng"
    },
    {
      "name": "Jiale An"
    },
    {
      "name": "Bohan Ma"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/afan6ew85dt5e.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pone.0358561",
  "fulltext_url": null,
  "id": "afan6ew85dt5e",
  "issns": [
    "1932-6203"
  ],
  "landing_url": "https://doi.org/10.1371/journal.pone.0358561",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Protein Degradation and Inhibitors"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cell processes/Cell cycle and cell division"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cell processes/Cell death/Apoptosis"
    ],
    [
      "plos",
      "/Medicine and health sciences/Gastroenterology and hepatology/Liver diseases/Hepatocellular carcinoma"
    ],
    [
      "plos",
      "/Medicine and health sciences/Nephrology/Renal cancer"
    ],
    [
      "plos",
      "/Medicine and health sciences/Oncology/Cancer treatment"
    ],
    [
      "plos",
      "/Medicine and health sciences/Oncology/Cancers and neoplasms"
    ],
    [
      "plos",
      "/Medicine and health sciences/Oncology/Cancers and neoplasms/Carcinoma/Hepatocellular carcinoma"
    ],
    [
      "plos",
      "/Medicine and health sciences/Oncology/Cancers and neoplasms/Gastrointestinal tumors/Hepatocellular carcinoma"
    ],
    [
      "plos",
      "/Medicine and health sciences/Oncology/Cancers and neoplasms/Genitourinary tract tumors/Bladder cancer"
    ],
    [
      "plos",
      "/Medicine and health sciences/Urology/Genitourinary cancers/Bladder cancer"
    ],
    [
      "plos",
      "/Research and analysis methods/Animal studies/Experimental organism systems/Animal models/Mouse models"
    ],
    [
      "plos",
      "/Research and analysis methods/Animal studies/Experimental organism systems/Model organisms/Mouse models"
    ],
    [
      "plos",
      "/Research and analysis methods/Model organisms/Mouse models"
    ]
  ],
  "openalex": "W7213947343",
  "pdf_url": "https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0358561&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-21",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/afan6ew85dt5e.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:43Z",
      "native_id": "10.1371/journal.pone.0358561",
      "source": "plos",
      "url": "https://doi.org/10.1371/journal.pone.0358561"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "plos:oncology",
      "subfield": "oncology"
    }
  ],
  "title": "PAK4-targeting PROTAC inhibits bladder cancer cell proliferation",
  "title_text": "PAK4-targeting PROTAC inhibits bladder cancer cell proliferation",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:43Z",
  "url": "https://research.draconitic.com/paper/afan6ew85dt5e",
  "venue": "PLOS One",
  "versions": []
}