ニシナ　タカシ   Nishina Takashi   仁科　隆史    所属   東邦大学  医学部 医学科    職種   講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Hypoxia-induced Wnt5a-secreting fibroblasts promote colon cancer progression.
掲載誌名	正式名：Nature Communication 略　 称：Nat Commun
掲載区分	国外
巻・号・頁	16(1),pp.3653
著者・共著者	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.
発行年月	2025/04/17
概要	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.
researchmap用URL	https://researchmap.jp/N_Takashi