2. Academic Validation
  3. Interferon-dependent SLC14A1+ cancer-associated fibroblasts promote cancer stemness via WNT5A in bladder cancer

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

  • Cancer Cell. 2022 Dec 12;40(12):1550-1565.e7. doi: 10.1016/j.ccell.2022.11.005.
Zikun Ma 1,  Xiangdong Li 1,  Yize Mao 2,  Chen Wei 3,  Zhuoli Huang 3,  Guibo Li 4,  Jianhua Yin 5,  Xiaoyu Liang 6,  Zhuowei Liu 7
Affiliations

Affiliations

  • 1 Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China; Department of Urology, Guangzhou 510060, China.
  • 2 Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China; Department of Pancreatobiliary Surgery, Guangzhou 510060, China.
  • 3 BGI-Shenzhen, Shenzhen 518083, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
  • 4 BGI-Shenzhen, Shenzhen 518083, China; Shenzhen Key Laboratory of Single-Cell Omics, BGI-Shenzhen, Shenzhen 518120, China.
  • 5 BGI-Shenzhen, Shenzhen 518083, China. Electronic address: yinjianhua@genomics.cn.
  • 6 Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China; Department of Radiation Oncology, Guangzhou 510060, China. Electronic address: liangxy1@sysucc.org.cn.
  • 7 Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China; Department of Urology, Guangzhou 510060, China. Electronic address: liuzhw@sysucc.org.cn.
PMID: 36459995 DOI: 10.1016/j.ccell.2022.11.005
Abstract

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.

Keywords

bladder cancer; cGAS-STING signaling; cancer associated fibroblasts; fibroblast subtype; interferon signaling; singlel-cell RNA sequencing; tumor immune microenvironment; tumor stemness; wnt/b-catenin.

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