FGF19-Activated Hepatic Stellate Cells Release ANGPTL4 that Promotes Colorectal Cancer Liver Metastasis.

Autor: Fan X; 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.; Chinese Medicine Guangdong Laboratory, Hengqin, Guangdong, 519031, China., Li B; 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., Zhang F; 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., Liu M; 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., Kwan HY; Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, 999077, China.; Institute of Research and Continuing Education, Hong Kong Baptist University, Shenzhen, 518000, China.; Institute of Systems Medicine and Health Sciences, Hong Kong Baptist University, Hong Kong, 999077, China., Liu Z; 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.; Chinese Medicine Guangdong Laboratory, Hengqin, Guangdong, 519031, China., Su T; 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.; Chinese Medicine Guangdong Laboratory, Hengqin, Guangdong, 519031, China.
Jazyk: angličtina
Zdroj: Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Adv Sci (Weinh)] 2024 Dec 24, pp. e2413525. Date of Electronic Publication: 2024 Dec 24.
DOI: 10.1002/advs.202413525
Abstrakt: Liver and lung are the most common metastatic sites in colorectal cancer (CRC), where the tumor microenvironment (TME) plays a crucial role in the progression and metastasis of CRC. Understanding the interactions between various types of cells in the TME can suggest innovative therapeutic strategies. Using single-cell RNA sequencing (scRNA-Seq) and clinical samples, fibroblast growth factor-19 (FGF19, rodent FGF15) is found to mediate a significant interaction between CRC cells and cancer-associated fibroblasts (CAFs), activating the hepatic stellate cells (HSCs)-to-CAFs differentiation. In various CRC metastatic mouse models, it is shown that FGF15 has a more pronounced effect on liver metastasis compared to pulmonary metastasis. More importantly, the differentially expressed genes (DEGs) are also identified from the RNA-Seq 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 in vivo. This study is among the first to demonstrate the impact of the FGF19/ANGPTL4 axis on CRCLM, offering a novel therapeutic strategy.
(© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
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