Reference - Detail
| RRC ID | 83793 |
|---|---|
| Author | Harada A, Yasumizu Y, Harada T, Fumoto K, Sato A, Maehara N, Sada R, Matsumoto S, Nishina T, Takeda K, Morii E, Kayama H, Kikuchi A. |
| Title | Hypoxia-induced Wnt5a-secreting fibroblasts promote colon cancer progression. |
| Journal | Nat Commun |
| Abstract |
Wnt5a, a representative Wnt ligand that activates the β-catenin-independent pathway, has been shown to promote tumorigenesis. However, it is unclear where Wnt5a is produced and how it affects colon cancer aggressiveness. In this study, we demonstrate that Wnt5a is expressed in fibroblasts near the luminal side of the tumor, and its depletion suppresses mouse colon cancer formation. To characterize the specific fibroblast subtype, a meta-analysis of human and mouse colon fibroblast single-cell RNA-seq data is performed. The results show that Wnt5a is expressed in hypoxia-induced inflammatory fibroblast (InfFib), accompanied by the activation of HIF2. Moreover, Wnt5a maintains InfFib through the suppression of angiogenesis mediated by soluble VEGF receptor1 (Flt1) secretion from endothelial cells, thereby inducing further hypoxia. InfFib also produces epiregulin, which promotes colon cancer growth. Here, we show that Wnt5a acts on endothelial cells, inducing a hypoxic environment that maintains InfFib, thereby contributing to colon cancer progression through InfFib. |
| Volume | 16(1) |
| Pages | 3653 |
| Published | 2025-4-17 |
| DOI | 10.1038/s41467-025-58748-9 |
| PII | 10.1038/s41467-025-58748-9 |
| PMID | 40246836 |
| PMC | PMC12006413 |
| MeSH | Animals Cell Hypoxia Cell Line, Tumor Colonic Neoplasms* / genetics Colonic Neoplasms* / metabolism Colonic Neoplasms* / pathology Disease Progression Endothelial Cells / metabolism Epiregulin / metabolism Fibroblasts* / metabolism Fibroblasts* / pathology Gene Expression Regulation, Neoplastic Humans Hypoxia* / metabolism Mice Mice, Inbred C57BL Neovascularization, Pathologic / metabolism Wnt-5a Protein* / genetics Wnt-5a Protein* / metabolism |
| IF | 12.121 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | News |
| Total number of mentions | 23 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | CACO-2(RCB0988) |