CAFs activated by YAP1 upregulate cancer matrix stiffness to mediate hepatocellular carcinoma progression DOI Creative Commons
Wei Yan, Guohui Xiao, Lijuan Wang

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 16, 2025

The stiffness of the matrix is closely related to progression hepatocellular carcinoma (HCC). Although direct targeting stromal rigidity in HCC remains a clinical challenge, cancer-associated fibroblasts (CAFs) are considered key contributors this process. Given heterogeneity CAFs, study explored relationship between specific CAF subsets and liver cancer stiffness, aiming identify novel therapeutic targets for patients. Single-cell sequencing datasets were leveraged cell types within characterize transcriptomic profiles CAFs. Prognostic analysis, utilizing Gene Expression Profiling Interactive Analysis (GEPIA) Cancer Genome Atlas (TCGA) datasets, assessed correlation stiffness-related genes patient outcomes. Pseudo-time analysis was applied trace developmental trajectories By calculating intercellular communication probabilities analyzing transcription factor activity, functions interactions different elucidated. Ontology (GO) used explore functional roles CAFs distinct Yes-associated protein 1 (YAP1) groups. Finally, cellular experiments animal further conducted validate hypotheses study. This identified subpopulations based on single-cell data analyzed transcriptional changes these subpopulations. Key findings include identification collagen type I alpha (COL1A1), III (COL3A1), lysyloxidase (LOX) as pivotal node during development. Moreover, expression inversely correlated with prognosis Notably, YAP1-positive subpopulation emerged primary contributor cancer. upregulates promotes tumor by activating signaling pathways such autophagy GTPase activity regulation. Cellular studies validated conclusion. uncovered subpopulation, particular, shown contribute upregulating relevant promoting through activation pathways.

Language: Английский

CAFs activated by YAP1 upregulate cancer matrix stiffness to mediate hepatocellular carcinoma progression DOI Creative Commons
Wei Yan, Guohui Xiao, Lijuan Wang

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 16, 2025

The stiffness of the matrix is closely related to progression hepatocellular carcinoma (HCC). Although direct targeting stromal rigidity in HCC remains a clinical challenge, cancer-associated fibroblasts (CAFs) are considered key contributors this process. Given heterogeneity CAFs, study explored relationship between specific CAF subsets and liver cancer stiffness, aiming identify novel therapeutic targets for patients. Single-cell sequencing datasets were leveraged cell types within characterize transcriptomic profiles CAFs. Prognostic analysis, utilizing Gene Expression Profiling Interactive Analysis (GEPIA) Cancer Genome Atlas (TCGA) datasets, assessed correlation stiffness-related genes patient outcomes. Pseudo-time analysis was applied trace developmental trajectories By calculating intercellular communication probabilities analyzing transcription factor activity, functions interactions different elucidated. Ontology (GO) used explore functional roles CAFs distinct Yes-associated protein 1 (YAP1) groups. Finally, cellular experiments animal further conducted validate hypotheses study. This identified subpopulations based on single-cell data analyzed transcriptional changes these subpopulations. Key findings include identification collagen type I alpha (COL1A1), III (COL3A1), lysyloxidase (LOX) as pivotal node during development. Moreover, expression inversely correlated with prognosis Notably, YAP1-positive subpopulation emerged primary contributor cancer. upregulates promotes tumor by activating signaling pathways such autophagy GTPase activity regulation. Cellular studies validated conclusion. uncovered subpopulation, particular, shown contribute upregulating relevant promoting through activation pathways.

Language: Английский

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