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  3. Epithelial cells activate fibroblasts to promote esophageal cancer development

Epithelial cells activate fibroblasts to promote esophageal cancer development

  • Cancer Cell. 2023 Mar 14;S1535-6108(23)00049-1. doi: 10.1016/j.ccell.2023.03.001.
Yamei Chen 1,  Shihao Zhu 1,  Tianyuan Liu 1,  Shaosen Zhang 1,  Junting Lu 1,  Wenyi Fan 1,  Lin Lin 1,  Tao Xiang 1,  Jie Yang 1,  Xuan Zhao 1,  Yiyi Xi 1,  Yuling Ma 1,  Guoyu Cheng 1,  Dongxin Lin 2,  Chen Wu 3
Affiliations

Affiliations

  • 1 Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
  • 2 Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; Key Laboratory of Cancer Genomic Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, China; Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou 510060, China. Electronic address: lindx@cicams.ac.cn.
  • 3 Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; Key Laboratory of Cancer Genomic Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, China; CAMS Oxford Institute, Chinese Academy of Medical Sciences, Beijing 100006, China. Electronic address: chenwu@cicams.ac.cn.
PMID: 36963399 DOI: 10.1016/j.ccell.2023.03.001
Abstract

Esophageal squamous-cell carcinoma (ESCC) develops through multistage epithelial Cancer formation, i.e., from normal epithelium, low- and high-grade intraepithelial neoplasia to invasive carcinoma. However, how the precancerous lesions progress to carcinoma remains elusive. Here, we report a comprehensive single-cell RNA Sequencing and spatial transcriptomic study of 79 multistage esophageal lesions from 29 patients with ESCC. We reveal a gradual and significant loss of ANXA1 expression in epithelial cells due to its transcription factor KLF4 suppression along the lesion progression. We demonstrate that ANXA1 is a ligand to formyl peptide receptor type 2 (FPR2) on fibroblasts that maintain fibroblast homeostasis. Loss of ANXA1 leads to uncontrolled transformation of normal fibroblasts into cancer-associated fibroblasts (CAFs), which can be enhanced by secreted TGF-β from malignant epithelial cells. Given the role of CAFs in Cancer, our study underscores ANXA1/FPR2 signaling as an important crosstalk mechanism between epithelial cells and fibroblasts in promoting ESCC.

Keywords

ANXA1; FPR2; cancer-associated fibroblast; esophageal cancer; precancerous lesions.

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