{
  "abstract": "Background Cancer-associated fibroblasts (CAFs) are key stromal components of the tumour microenvironment (TME) that profoundly influence tumour progression. However, CAFs exhibit pronounced phenotypic and functional heterogeneity, and whether conserved CAF subtypes with shared functional hallmarks exist across different cancer types remains unclear.Objective We sought to uncover universal CAF subtypes that transcend tumour origins, defining their core molecular signatures and pro-tumorigenic functions within the TME.Design We constructed a pan-cancer CAF atlas through single-cell transcriptomic analysis of 554 specimens across 14 cancer types. To validate the findings, we performed further functional analyses, including in vitro migration and invasion assays, in vivo lymphatic metastasis models and mechanistic studies focusing on candidate signalling pathways.Results We identified a conserved syndecan 1 (SDC1) + CAF subset associated with advanced tumour stage and poor outcomes. These CAFs enhanced tumour cell migration and invasion in vitro and promoted lymphatic metastasis in vivo. This effect is mediated through connective tissue growth factor (CTGF) secretion, which activates fibroblast growth factor receptor 3 (FGFR3) signalling in tumour cells to induce epithelial-mesenchymal transition (EMT). Blocking CTGF or FGFR3 signalling abrogated these effects. We also found that kruppel like factor 6 (KLF6) directly regulates CTGF in SDC1+ CAFs, establishing a complete KLF6-CTGF-FGFR3 metastatic axis.Conclusions Our study establishes SDC1 + CAFs as a universal, metastasis-promoting CAF subset across multiple cancer types and uncovers a novel KLF6-CTGF-FGFR3 axis that drives EMT and tumour dissemination. These findings provide mechanistic insight into CAF-tumour cell crosstalk and highlight actionable stromal targets for anti-metastatic therapies across diverse malignancies.",
  "authors": [
    {
      "affiliations": [
        "State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China",
        "Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China"
      ],
      "name": "Guan-Feng Gao"
    },
    {
      "affiliations": [
        "Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha, China",
        "Third Xiangya Hospital, Central South University, Changsha, China"
      ],
      "name": "Zhao-Hui Ruan"
    },
    {
      "affiliations": [
        "State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China",
        "Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China"
      ],
      "name": "Shi-Bo Zhang"
    },
    {
      "affiliations": [
        "State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China",
        "Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China"
      ],
      "name": "Shuai He"
    },
    {
      "affiliations": [
        "State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China",
        "Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China"
      ],
      "name": "Yi-Qi Li"
    },
    {
      "affiliations": [
        "State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China",
        "Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China"
      ],
      "name": "Jin-Li Lyu"
    },
    {
      "affiliations": [
        "State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China",
        "Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China"
      ],
      "name": "Yang Liu"
    },
    {
      "affiliations": [
        "Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China"
      ],
      "name": "Xing-Liang Tan"
    },
    {
      "affiliations": [
        "Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China"
      ],
      "name": "Yan-Jun Wang"
    },
    {
      "affiliations": [
        "Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China"
      ],
      "name": "Zhuo-Wei Liu"
    },
    {
      "affiliations": [
        "Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China"
      ],
      "name": "Guang-Zhao Lv"
    },
    {
      "affiliations": [
        "Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China"
      ],
      "name": "Gong Chen"
    },
    {
      "affiliations": [
        "Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China"
      ],
      "name": "Jie-Hai Yu"
    },
    {
      "affiliations": [
        "State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China",
        "Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China"
      ],
      "name": "Pan-Pan Wei"
    },
    {
      "affiliations": [
        "Research Center of Cancer Diagnosis and Therapy, Jinan University First Affiliated Hospital, Guangzhou, China"
      ],
      "name": "Jian-Fu Zhao"
    },
    {
      "affiliations": [
        "Research Center of Cancer Diagnosis and Therapy, Jinan University First Affiliated Hospital, Guangzhou, China"
      ],
      "name": "Zhi-Ting Sun"
    },
    {
      "affiliations": [
        "Beijing Neurosurgical Institute, Capital Medical University, Beijing, China",
        "Chinese Glioma Genome Atlas (CGGA) Network and Asian Glioma Genome Atlas (AGGA) Network, Beijing, China"
      ],
      "name": "Zheng Zhao"
    },
    {
      "affiliations": [
        "Institute of Pathology & Southwest Cancer Center, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University, Chongqing, China",
        "Chongqing Yuyue Scientific Research Center for Pathology, Chongqing Institute of Advanced Pathology, Jinfeng Laboratory, Chongqing, China"
      ],
      "name": "Yu Shi"
    },
    {
      "affiliations": [
        "Department of Intensive Care Unit, Sun Yat-sen University Cancer Center, Guangzhou, China"
      ],
      "name": "Wei Liao"
    },
    {
      "affiliations": [
        "Department of Head and Neck Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China"
      ],
      "name": "Shu-Wei Chen"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China"
      ],
      "name": "Nu Zhang"
    },
    {
      "affiliations": [
        "Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, MOE Key Laboratory of Gene Function and Regulation, School of Life Sciences, Sun Yat-Sen University, Guangzhou, China"
      ],
      "name": "Dong-Ming Kuang"
    },
    {
      "affiliations": [
        "Department of Clinical Oncology, The University of Hong Kong, Hong Kong, China"
      ],
      "name": "Xin-Yuan Guan"
    },
    {
      "affiliations": [
        "State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China"
      ],
      "name": "Rou-Jun Peng"
    },
    {
      "affiliations": [
        "Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China"
      ],
      "name": "Mu-Yan Cai"
    },
    {
      "affiliations": [
        "Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China"
      ],
      "name": "Kai Yao"
    },
    {
      "affiliations": [
        "Institute of Pathology & Southwest Cancer Center, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University, Chongqing, China",
        "Chongqing Yuyue Scientific Research Center for Pathology, Chongqing Institute of Advanced Pathology, Jinfeng Laboratory, Chongqing, China"
      ],
      "name": "Xiu-Wu Bian"
    },
    {
      "affiliations": [
        "Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China"
      ],
      "name": "Pei-Rong Ding"
    },
    {
      "affiliations": [
        "State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China",
        "Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China"
      ],
      "name": "Chun-Ling Luo"
    },
    {
      "affiliations": [
        "State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China",
        "Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China",
        "Department of Medical Oncology, National Cancer Centre Singapore, Singapore",
        "Sun Yat-sen University Institute of Advanced Studies Hong Kong, Science Park, Hong Kong, People's Republic of China",
        "Department of Clinical Oncology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, People's Republic of China"
      ],
      "name": "Jin-Xin Bei"
    }
  ],
  "title": "SDC1+ CAFs secreting CTGF drive tumour metastasis via FGFR3 signalling in cancers",
  "uid": "ecd0e956-4526-5667-b9be-1ad44d759a26"
}