小柯机器人

中国医学科学院吴晨等研究组合作发现上皮细胞激活成纤维细胞促进食管癌发展。相关论文于2023年3月23日发表在《癌细胞》杂志上。

他们报道了一项全面的单细胞RNA测序和空间转录组学研究，研究了29例食管鳞状细胞癌(ESCC)患者的79个多级食管病变。他们发现，在病变进展过程中，由于转录因子KLF4的抑制，上皮细胞中ANXA1的表达逐渐而显著地丧失。他们证明了ANXA1是成纤维细胞上甲酰基肽受体2型(FPR2)的配体，维持成纤维细胞的稳态。

ANXA1的缺失导致正常成纤维细胞不受控制地转化为癌症相关成纤维细胞(CAFs)，这可以通过恶性上皮细胞分泌TGF-β而增强。鉴于CAFs在癌症中的作用，他们的研究强调了ANXA1/FPR2信号通路是上皮细胞和成纤维细胞之间促进ESCC的重要串扰机制。

据介绍，ESCC是由正常上皮细胞、低级别和高级别上皮内瘤变到浸润性癌的多阶段上皮细胞癌形成的。然而，癌前病变是如何发展为癌的仍然是不清楚的。

附：英文原文

Title: Epithelial cells activate fibroblasts to promote esophageal cancer development

Author: Yamei Chen, Shihao Zhu, Tianyuan Liu, Shaosen Zhang, Junting Lu, Wenyi Fan, Lin Lin, Tao Xiang, Jie Yang, Xuan Zhao, Yiyi Xi, Yuling Ma, Guoyu Cheng, Dongxin Lin, Chen Wu

Issue&Volume: 2023-03-23

Abstract: Esophageal squamous-cell carcinoma (ESCC) develops through multistage epithelial cancerformation, i.e., from normal epithelium, low- and high-grade intraepithelial neoplasiato invasive carcinoma. However, how the precancerous lesions progress to carcinomaremains elusive. Here, we report a comprehensive single-cell RNA sequencing and spatialtranscriptomic 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 alongthe lesion progression. We demonstrate that ANXA1 is a ligand to formyl peptide receptortype 2 (FPR2) on fibroblasts that maintain fibroblast homeostasis. Loss of ANXA1 leadsto uncontrolled transformation of normal fibroblasts into cancer-associated fibroblasts(CAFs), which can be enhanced by secreted TGF-β from malignant epithelial cells. Giventhe role of CAFs in cancer, our study underscores ANXA1/FPR2 signaling as an importantcrosstalk mechanism between epithelial cells and fibroblasts in promoting ESCC.

DOI: 10.1016/j.ccell.2023.03.001

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00049-1

Cancer Cell：《癌细胞》，创刊于2002年。隶属于细胞出版社，最新IF：38.585
官方网址：https://www.cell.com/cancer-cell/home
投稿链接：https://www.editorialmanager.com/cancer-cell/default.aspx