Bifidobacterium adolescentis orchestrates CD143^(+)cancer-associated fibroblasts to suppress colorectal tumorigenesis by Wnt signaling-regulated GAS1
作者机构：Department of GastroenterologySir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhouZhejiangP. R. China Institute of GastroenterologyZhejiang UniversityHangzhouZhejiangP. R. China Cancer CenterZhejiang UniversityHangzhouZhejiangP. R. China Research Center of Prevention and Treatment of Senescent DiseaseSchool of Medicine Zhejiang UniversityHangzhouZhejiangP. R. China Department of GastroenterologySecond Affiliated Hospital of Zhejiang University School of MedicineHangzhouZhejiangP. R. China
出 版 物：《Cancer Communications》 (癌症通讯（英文）)
年 卷 期：2023年第43卷第9期
页 面：1027-1047页
核心收录：
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
基 金：National Natural Science Foundation of China,Grant/Award Numbers:82072623,82270573,82203618 Zhejiang Province Natural Science Foundation,Grant/Award Number:LZ22H160002 Zhejiang Province Medicine and Health Science and Technology Project,Grant/Award Numbers:2023KY722,2023KY785
主 题：Bifidobacterium adolescentis cancer-associated fibroblast colorectal cancer GAS1 microbiota single-cell RNA sequencing Wnt/β-catenin signaling
摘 要：Background The interplay between gut microbiota and tumor microenvironment(TME)in the pathogenesis of colorectal cancer(CRC)is not well ***,we elucidated the functional role of Bifidobacterium adolescentis(B.a)on CRC and investigated its possible mechanism on the manipulation of cancer-associated fibroblasts(CAFs)in *** Different CRC animal models and various cell line models were established to explore the function of B.a on *** single-cell RNA sequencing(scRNA-seq)or flow cytometry was used to detect the cell subsets in the TME of *** blot,quantitative real-time polymerase chain reaction(qRT-PCR),or immunofluorescence staining were performed to examine the activation of Wnt signaling and growth arrest specific 1(GAS1)on CD143+*** immunoprecipitation quantitative real-time PCR(CHIP-qPCR)was performed to investigate the regulation of transcription factor 4(TCF4)on ***-immunofluorescence assay examined the expression level of CD143 and GAS1 on tissue *** We found that B.a abundance was significantly reduced in CRC patients from two independent cohorts and the bacteria database of *** with B.a suppressed ApcMin/+spontaneous or AOM/DSS-induced tumorigenesis in ***-seq revealed that B.a facilitated a subset of CD143+CAFs by inhibiting the infiltration of Th2 cells,while promoting the TNF-alpha+B cells in ***143+CAFs highly expressed GAS1 and exhibited tumor suppressive ***,GAS1 was activated by the Wnt/β-catenin signaling in CD143+CAFs.B.a abundance was correlated with the expression level of CD143 and *** level of CD143+CAFs predicted the better survival outcome in CRC *** These results highlighted that B.a induced a new subset of CD143+CAFs by Wnt signaling-regulated GAS1 to suppress tumorigenesis and provided a novel therapeutic target for probiotic-based modulation of TME in CRC.
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