The Hedgehog Pathway Promotes Monocytes Infiltration Through CCL20-CCR6 Axis in Hepatocellular Carcinoma

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Hepatocellular carcinoma (HCC) is a major global cancer.
• Tumor microenvironment, including inflammation and fibrosis, is critical in HCC.
• The Hedgehog (Hh) signaling pathway plays a role in HCC progression.

Purpose of the Study:

• Investigate the Hh pathway's role in HCC-monocyte interactions.
• Identify key molecules mediating monocyte recruitment in HCC.
• Explore therapeutic potential targeting the Hh pathway in HCC.

Main Methods:

• Transwell migration assays to assess monocyte migration.
• Luciferase reporter and chromatin immunoprecipitation assays to confirm gene regulation.
• Xenograft mouse models to evaluate tumor growth and immune cell infiltration.
• Analysis of clinical samples for gene expression correlation and survival outcomes.

Main Results:

• GLI1, an Hh pathway effector, promotes THP-1 monocyte migration.
• CCL20, regulated by Hh pathway in HCC cells, mediates migration via CCR6 on monocytes.
• GLI1 directly binds to the CCL20 promoter region.
• Inhibition of GLI1 or CCL20 reduced tumor growth and monocyte infiltration in vivo.
• High CCL20 expression correlates with poor patient survival.

Conclusions:

• The Hh pathway in HCC promotes monocyte infiltration through the CCL20-CCR6 axis.
• This pathway represents a potential therapeutic target for HCC treatment.
• Understanding this interaction offers insights into HCC progression and immune evasion.