Hypoxia-induced Wnt5a-secreting fibroblasts promote colon cancer progression
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View abstract on PubMed
Summary
This summary is machine-generated.Wnt5a protein, produced by inflammatory fibroblasts, fuels colon cancer growth by creating a hypoxic tumor microenvironment. Depleting Wnt5a suppresses tumor formation, offering a potential therapeutic target.
Area Of Science
- Oncology
- Cell Biology
- Cancer Research
Background
- Wnt5a is a Wnt ligand activating β-catenin-independent pathways and promoting tumorigenesis.
- Its production site and impact on colon cancer aggressiveness remain unclear.
Purpose Of The Study
- To investigate the source of Wnt5a production in colon cancer.
- To elucidate the mechanism by which Wnt5a influences colon cancer progression.
Main Methods
- Meta-analysis of human and mouse colon fibroblast single-cell RNA-seq data.
- In vivo studies involving Wnt5a depletion in mouse models.
- Analysis of fibroblast-endothelial cell interactions and molecular signaling pathways.
Main Results
- Wnt5a is expressed in fibroblasts near the tumor's luminal side, identified as hypoxia-induced inflammatory fibroblasts (InfFib) with activated HIF2.
- Wnt5a maintains InfFib by suppressing angiogenesis via Flt1 secretion from endothelial cells, inducing hypoxia.
- InfFib produces epiregulin, promoting colon cancer growth.
Conclusions
- Wnt5a drives colon cancer progression by inducing a hypoxic microenvironment that sustains InfFib.
- Targeting Wnt5a or InfFib may represent a novel therapeutic strategy for colon cancer.
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