小柯机器人

中山大学肿瘤防治中心刘卓炜研究团队探明干扰素依赖性SLC14A1+，癌症相关成纤维细胞(CAFs)通过WNT5A促进膀胱癌(BC)的癌干性。这一研究成果于2022年12月1日发表在国际顶尖学术期刊《癌细胞》上。

他们使用BC患者样本的单细胞RNA测序报告了一个以尿素转运体SLC14A1过表达为特征的CAF亚群。该群体由干扰素信号诱导，并通过WNT5A旁分泌途径赋予BC细胞干性。肿瘤细胞中cGAS-STING信号的激活驱动干扰素的产生，从而揭示了cGAS-STING信号与SLC14A1+ CAF分化之间的联系。此外，通过靶向STAT1或STING抑制SLC14A1+ CAF的形成可使肿瘤细胞对化疗敏感。更重要的是，肿瘤内SLC14A1+ CAFs比例高的BC患者表现出癌症分期无关的不良预后，对新辅助化疗或免疫治疗的应答率更低。

据介绍，CAF在癌症治疗反应和患者预后中发挥作用。CAF表现出表型和功能的异质性，在不同组织来源的肿瘤中差异很大。

附：英文原文

Title: Interferon-dependent SLC14A1+ cancer-associated fibroblasts promote cancer stemness via WNT5A in bladder cancer

Author: Zikun Ma, Xiangdong Li, Yize Mao, Chen Wei, Zhuoli Huang, Guibo Li, Jianhua Yin, Xiaoyu Liang, Zhuowei Liu

Issue&Volume: 2022-12-01

Abstract: Cancer-associated fibroblasts (CAFs) play a role in response to cancer treatment andpatient prognosis. CAFs show phenotypic and functional heterogeneity and differ widelyin tumors of different tissue origin. Here, we use single-cell RNA sequencing of bladdercancer (BC) patient samples and report a CAF subpopulation characterized by overexpressionof the urea transporter SLC14A1. This population is induced by interferon signalingand confers stemness to BC cells via the WNT5A paracrine pathway. Activation of cGAS-STINGsignaling in tumor cells drives interferon production, thereby revealing a link betweencGAS-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 neoadjuvantchemotherapy or immunotherapy.

DOI: 10.1016/j.ccell.2022.11.005

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(22)00552-9

Cancer Cell：《癌细胞》，创刊于2002年。隶属于细胞出版社，最新IF：38.585
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