{
  "abstract": "Background Liver metastasis is a major cause of mortality in patients with colorectal cancer (CRC). Understanding how CRC cells influence the formation of hepatic premetastatic niches (PMNs) is crucial for developing targeted therapies.Objective We aimed to elucidate the underlying mechanism by which extracellular vesicles (EVs) derived from CRC cells with high liver metastatic capacity facilitate the formation of hepatic PMNs.Design CRC cells with high metastatic potential were selected using a liver metastasis mouse model through two rounds of splenic injections. The role of EVs secreted by CRC cells in the liver was investigated using lipidomics and single-cell sequencing. Clinical significance was evaluated by tumour samples from patients with CRC.Results EVs derived from highly metastatic CRC cells facilitate the formation of PMNs by driving hepatic lipid accumulation. The upregulation of fatty acid (FA) synthesis in CRC cells leads to significantly increased levels of prosteatogenic lipids in EVs, promoting hepatic lipid accumulation. Inhibition of hepatic lipid accumulation reduces the prometastatic capability of EVs secreted by highly metastatic CRC cells. Moreover, EVs are primarily taken up by Kupffer cells, where they induce tumour necrosis factor alpha secretion, further driving hepatic lipid accumulation. In patients with late-stage CRC, CRC cells exhibit elevated FA synthesis, which contributes to hepatic lipid accumulation. Notably, suppressing FA synthesis in CRC patient-derived organoids alleviates hepatic lipid accumulation and reduces liver metastasis.Conclusion Inhibition of FA synthesis in CRC cells with high metastatic potential reduces hepatic lipid accumulation and subsequent metastasis, highlighting a new strategy for preventing liver metastasis.",
  "authors": [
    {
      "affiliations": [
        "Department of Biotherapy, Oxidative Stress Research Center, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital and West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China"
      ],
      "name": "Jiangjun Cao"
    },
    {
      "affiliations": [
        "Department of Biotherapy, Oxidative Stress Research Center, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital and West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China",
        "Frontiers Medical Center, Tianfu Jincheng Laboratory, Chengdu, China"
      ],
      "name": "Siyuan Qin"
    },
    {
      "affiliations": [
        "Department of Biotherapy, Oxidative Stress Research Center, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital and West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China"
      ],
      "name": "Bowen Li"
    },
    {
      "affiliations": [
        "Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospita, School of Medicine, Zhejiang University, Hangzhou, China"
      ],
      "name": "Zhe Zhang"
    },
    {
      "affiliations": [
        "Department of Biotherapy, Oxidative Stress Research Center, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital and West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China"
      ],
      "name": "Peng Miao"
    },
    {
      "affiliations": [
        "Department of Biotherapy, Oxidative Stress Research Center, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital and West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China"
      ],
      "name": "Han Yan"
    },
    {
      "affiliations": [
        "School of Medicine, Wuhan University of Science and Technology, Wuhan, China"
      ],
      "name": "Jiufei Duan"
    },
    {
      "affiliations": [
        "Department of Pathophysiology, Zunyi Medical University, Zunyi, China"
      ],
      "name": "Bo He"
    },
    {
      "affiliations": [
        "Department of Oncology, the Second Hospital Affiliated to Air Force Medical University, Xi'an, China"
      ],
      "name": "Kai He"
    },
    {
      "affiliations": [
        "Department of Biotherapy, Oxidative Stress Research Center, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital and West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China"
      ],
      "name": "Peilan Peng"
    },
    {
      "affiliations": [
        "Department of Anorectal Surgery, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China"
      ],
      "name": "Lei Li"
    },
    {
      "affiliations": [
        "Department of central laboratory, The first affiliated Hospital, Ningbo University, Ningbo, China"
      ],
      "name": "Hao Jiang"
    },
    {
      "affiliations": [
        "Department of Biotherapy, Oxidative Stress Research Center, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital and West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China"
      ],
      "name": "Zizhuo Xie"
    },
    {
      "affiliations": [
        "West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China"
      ],
      "name": "Jingwen Jiang"
    },
    {
      "affiliations": [
        "Department of Central Laboratory, Ningbo University, Ningbo, China"
      ],
      "name": "Xia Chen"
    },
    {
      "affiliations": [
        "Department of General Surgery and Colorectal Cancer Center, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China"
      ],
      "name": "Hai-Ning Chen"
    },
    {
      "affiliations": [
        "Department of Biotherapy, Oxidative Stress Research Center, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital and West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China",
        "Frontiers Medical Center, Tianfu Jincheng Laboratory, Chengdu, China"
      ],
      "name": "Canhua Huang"
    }
  ],
  "title": "Extracellular vesicle-induced lipid dysregulation drives liver premetastatic niche formation in colorectal cancer",
  "uid": "d9561867-c4c6-5ca4-9179-e6f472a1a333"
}