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RRC ID 83793
著者 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.
タイトル Hypoxia-induced Wnt5a-secreting fibroblasts promote colon cancer progression.
ジャーナル 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.
巻・号 16(1)
ページ 3653
公開日 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
リソース情報
ヒト・動物細胞 CACO-2(RCB0988)