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Understanding the interactions between various types of cells in the TME can suggest innovative therapeutic strategies. Using single\u2010cell RNA sequencing (scRNA\u2010Seq) and clinical samples, fibroblast growth factor\u201019 (FGF19, rodent FGF15) is found to mediate a significant interaction between CRC cells and cancer\u2010associated fibroblasts (CAFs), activating\u00a0the hepatic stellate cells (HSCs)\u2010to\u2010CAFs differentiation. In various CRC metastatic mouse models, it is shown that FGF15\u00a0has a more pronounced effect on liver metastasis compared to pulmonary metastasis. More importantly, the differentially expressed genes (DEGs) are also identified from the RNA\u2010Seq dataset upon the activation of HSCs by FGF19 and compared the DEGs in matched primary and metastatic mRNA samples from patients with CRC liver metastasis (CRCLM), it is found that the ANGPTL4 gene is significantly associated with HSCs activation. Different mouse models also demonstrated the impact of the FGF19\/ANGPTL4 axis on the severity of CRCLM. Importantly, disruption of this axis significantly inhibits CRCLM\u00a0in vivo. This study is among the first to demonstrate the impact of the FGF19\/ANGPTL4 axis on CRCLM, offering a novel therapeutic strategy.<\/jats:p>","DOI":"10.1002\/advs.202413525","type":"journal-article","created":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T03:06:13Z","timestamp":1735009573000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["FGF19\u2010Activated Hepatic Stellate Cells Release ANGPTL4 that Promotes Colorectal Cancer Liver Metastasis"],"prefix":"10.1002","volume":"12","author":[{"given":"Xueying","family":"Fan","sequence":"first","affiliation":[{"name":"State Key Laboratory of Traditional Chinese Medicine Syndrome Guangdong Key Laboratory for Translational Cancer Research of Chinese Medicine International Institute for Translational Chinese Medicine Guangzhou University of Chinese Medicine  Guangzhou Guangdong 510006 China"},{"name":"Chinese Medicine Guangdong Laboratory  Hengqin Guangdong 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