CD168+ macrophages promote hepatocellular carcinoma tumor stemness and progression through TOP2A/β-catenin/YAP1 axis
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Updated: Aug 2, 2026

Isolation of CD133+ Liver Stem Cells for Clonal Expansion
Published on: October 10, 2011
Hai-Chao Zhao1,2, Chang-Zhou Chen2, Yan-Zhang Tian3
1Third Hospital of Shanxi Medical University, Shanxi Academy of Medical Sciences, Taiyuan 030032, China.
Abstract:
Liver cancer stem-like cells (LCSCs) are the main cause of heterogeneity and poor prognosis in hepatocellular carcinoma (HCC). In this study, we aimed to explore the origin of LCSCs and the role of the TOP2A/β-catenin/YAP1 axis in tumor stemness and progression. Using single-cell RNA-seq analysis, we identified TOP2A+CENPF+ LCSCs, which were mainly regulated by CD168+ M2-like macrophages. Furthermore, spatial location analysis and fluorescent staining confirmed that LCSCs were enriched at tumor margins, constituting the spatial heterogeneity of HCC. Mechanistically, TOP2A competitively binds to β-catenin, leading to disassociation of β-catenin from YAP1, promoting HCC stemness and overgrowth. Our study provides valuable insights into the spatial transcriptome heterogeneity of the HCC microenvironment and the critical role of TOP2A/β-catenin/YAP1 axis in HCC stemness and progression.
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