CAFs activated by YAP1 upregulate cancer matrix stiffness to mediate hepatocellular carcinoma progression

作者：Wei Yan, Guohui Xiao, Lijuan Wang, Yan Zhou, Fa Yang, Kuanhou Mou · 发表于：Journal of Translational Medicine · 年份：2025 · DOI：10.1186/s12967-025-06325-5 · 被引用次数：16 · 研究领域：Hippo pathway signaling and YAP/TAZ、Cancer Cells and Metastasis、Single-cell and spatial transcriptomics

BACKGROUND: The stiffness of the matrix is closely related to the progression of hepatocellular carcinoma (HCC). Although direct targeting of stromal rigidity in HCC remains a clinical challenge, cancer-associated fibroblasts (CAFs) are considered key contributors to this process. Given the heterogeneity of CAFs, this study explored the relationship between specific CAF subsets and liver cancer matrix stiffness, aiming to identify novel therapeutic targets for HCC patients. METHODS: Single-cell sequencing datasets were leveraged to identify cell types within liver cancer and characterize the transcriptomic profiles of CAFs. Prognostic analysis, utilizing the Gene Expression Profiling Interactive Analysis (GEPIA) and The Cancer Genome Atlas (TCGA) liver cancer datasets, assessed the correlation between matrix stiffness-related genes and HCC patient outcomes. Pseudo-time analysis was applied to trace the developmental trajectories of CAFs. By calculating intercellular communication probabilities and analyzing transcription factor activity, the functions and interactions of different CAF subsets were elucidated. Gene Ontology (GO) analysis was used to explore the functional roles of CAFs in distinct Yes-associated protein 1 (YAP1) groups. Finally, cellular experiments and animal experiments were further conducted to validate the hypotheses of this study. RESULTS: This study identified CAF subpopulations based on single-cell sequencing data and analyzed transcriptional changes wi...