{
  "abstract": "The prognosis for advanced colorectal cancer (CRC) remains poor, and 5-fluorouracil (5-FU)-based chemotherapy is the primary treatment option. Understanding the mechanisms that limit the effectiveness of this therapy is therefore clinically important. However, the molecular drivers of acquired chemotherapy resistance in advanced CRC are not fully understood. Here we show that expression of PDZ-LIM domain-containing protein 4 (PDLIM4) is significantly upregulated following neoadjuvant chemotherapy in patients with advanced CRC, and that its expression level is closely associated with patient prognosis. PDLIM4 promotes acquired resistance to 5-FU by enhancing the stemness, anti-apoptotic capacity, and drug efflux of colorectal cancer stem cells. Mechanistically, PDLIM4 facilitates the accumulation of sphingolipids, particularly sphingomyelin, and regulates the PI3K/Akt signaling pathway. These findings identify PDLIM4 as a potential biomarker and therapeutic target for overcoming chemoresistance in advanced colorectal cancer, opening new avenues for future treatment strategies.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China",
    "Minimally Invasive Center for Hepatobiliary and Pancreatic Surgery, Zhuhai Hospital of Guangdong Provincial Hospital of Chinese Medicine, Zhuhai, China",
    "Department of Hepatobiliary, Pancreatic and Splenic surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China",
    "Department of Cell-Gene Therapy Translational Medicine Research Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China",
    "Department of Hepatic Surgery, Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China",
    "Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China",
    "Department of Human Anatomy, Histology and Embryology, Zhuhai Campus of Zunyi Medical University, Zhuhai, China",
    "Department of Obstetrics, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China",
    "Department of Medical Oncology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Yingqiu Song"
    },
    {
      "affs": [
        2
      ],
      "name": "Zhiyong Xiong"
    },
    {
      "affs": [
        0
      ],
      "name": "Dagui Zhou"
    },
    {
      "affs": [
        3
      ],
      "name": "Ya-Han Ren"
    },
    {
      "affs": [
        0
      ],
      "name": "Qianhui Liu"
    },
    {
      "affs": [
        4
      ],
      "name": "Xu Lu"
    },
    {
      "affs": [
        5
      ],
      "name": "Jinyang Wang"
    },
    {
      "affs": [
        6
      ],
      "name": "Ziyan Zhu"
    },
    {
      "affs": [
        4
      ],
      "name": "Yongsheng Tang"
    },
    {
      "affs": [
        0
      ],
      "name": "Hao Li"
    },
    {
      "affs": [
        3
      ],
      "name": "Manqiu Kang"
    },
    {
      "affs": [
        7
      ],
      "name": "Ling Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaofeng Yang"
    },
    {
      "affs": [
        8
      ],
      "name": "Tiantian Wang",
      "orcid": "0000-0003-0336-091X"
    },
    {
      "affs": [
        3
      ],
      "name": "Changchang Jia",
      "orcid": "0000-0002-5243-0008"
    },
    {
      "affs": [
        0
      ],
      "name": "Jiafeng Fang",
      "orcid": "0000-0002-1570-8824"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7fm6ca2f0mgwj.bib",
  "cited_by": 0,
  "doi": "10.1038/s42003-026-10627-9",
  "fulltext_url": "https://doi.org/10.1038/s42003-026-10627-9",
  "id": "7fm6ca2f0mgwj",
  "issns": [
    "2399-3642"
  ],
  "landing_url": "https://doi.org/10.1038/s42003-026-10627-9",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "lcc",
      "QH301-705.5"
    ],
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      "openalex",
      "2730|Cancer Cells and Metastasis"
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  "openalex": "W7168046566",
  "pdf_url": null,
  "pmcid": "PMC13736959",
  "pmid": "42436219",
  "published": "2026-07-01",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/7fm6ca2f0mgwj.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T14:21:02Z",
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cancer Cells and Metastasis",
      "subfield": "oncology"
    }
  ],
  "title": "PDLIM4 increases sphingolipid accumulation to promote cancer stem cell characteristics and chemotherapy resistance in colorectal cancer",
  "title_text": "PDLIM4 increases sphingolipid accumulation to promote cancer stem cell characteristics and chemotherapy resistance in colorectal cancer",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:22:17Z",
  "url": "https://research.draconitic.com/paper/7fm6ca2f0mgwj",
  "venue": "Communications Biology",
  "versions": []
}