癌症
癌症研究
WNT5A型
癌细胞
癌症干细胞
癌相关成纤维细胞
旁分泌信号
膀胱癌
肿瘤微环境
干扰素
人口
免疫疗法
生物
医学
免疫学
内科学
Wnt信号通路
信号转导
细胞生物学
肿瘤细胞
受体
环境卫生
作者
Zhiyuan Ma,Xiangdong Li,Yijun Mao,Wei Chen,Zhuoli Huang,Guibo Li,Jianhua Yin,Xiaoyu Liang,Zhuowei Liu
出处
期刊:Cancer Cell
[Elsevier]
日期:2022-12-01
卷期号:40 (12): 1550-1565.e7
被引量:48
标识
DOI:10.1016/j.ccell.2022.11.005
摘要
Cancer-associated fibroblasts (CAFs) play a role in response to cancer treatment and patient prognosis. CAFs show phenotypic and functional heterogeneity and differ widely in tumors of different tissue origin. Here, we use single-cell RNA sequencing of bladder cancer (BC) patient samples and report a CAF subpopulation characterized by overexpression of the urea transporter SLC14A1. This population is induced by interferon signaling and confers stemness to BC cells via the WNT5A paracrine pathway. Activation of cGAS-STING signaling in tumor cells drives interferon production, thereby revealing a link between cGAS-STING signaling and SLC14A1+ CAF differentiation. Furthermore, the inhibition of SLC14A1+ CAF formation via targeting of STAT1 or STING sensitizes tumor cells to chemotherapy. More important, BC patients with high proportions of intratumoral SLC14A1+ CAFs show cancer stage-independent poor outcome and a worse response rate to neoadjuvant chemotherapy or immunotherapy.
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