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CD168+ macrophages promote hepatocellular carcinoma tumor stemness and progression through TOP2A/β-catenin/YAP1 axis.

Hai-Chao Zhao1,2, Chang-Zhou Chen2, Yan-Zhang Tian3

  • 1Third Hospital of Shanxi Medical University, Shanxi Academy of Medical Sciences, Taiyuan 030032, China.

Iscience
|June 5, 2023
PubMed
Summary

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This summary is machine-generated.

Liver cancer stem cells (LCSCs) drive hepatocellular carcinoma (HCC) progression. This study identifies TOP2A+ LCSCs regulated by macrophages, revealing the TOP2A/β-catenin/YAP1 axis as crucial for HCC stemness and tumor growth.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Liver cancer stem-like cells (LCSCs) contribute significantly to hepatocellular carcinoma (HCC) heterogeneity and poor patient outcomes.
  • Understanding the origin and regulatory mechanisms of LCSCs is critical for developing effective HCC therapies.

Purpose of the Study:

  • To investigate the origin and spatial distribution of LCSCs within the HCC microenvironment.
  • To elucidate the role of the TOP2A/β-catenin/YAP1 signaling axis in regulating LCSC stemness and HCC progression.

Main Methods:

  • Single-cell RNA-seq analysis to identify LCSC subtypes and their regulatory cells.
  • Spatial location analysis and fluorescent staining to determine LCSC enrichment zones.
  • Mechanistic studies to explore the interaction between TOP2A, β-catenin, and YAP1.
Keywords:
CancerMolecular interactionSpecialized functions of cellsTranscriptomics

Related Experiment Videos

Main Results:

  • Identification of TOP2A+CENPF+ LCSCs, predominantly regulated by CD168+ M2-like macrophages.
  • Demonstration that LCSCs are spatially enriched at tumor margins, contributing to HCC heterogeneity.
  • Elucidation of TOP2A's mechanism: competitive binding to β-catenin, disrupting the β-catenin/YAP1 complex and promoting stemness.

Conclusions:

  • LCSCs are a key driver of HCC stemness and progression, with distinct spatial heterogeneity.
  • The TOP2A/β-catenin/YAP1 axis represents a novel therapeutic target for HCC.
  • This research offers insights into the complex HCC tumor microenvironment and LCSC regulation.