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癌症相关成纤维细胞衍生的SULF1通过TGFBR3介导的TGF-β信号通路促进胃癌转移和顺铂耐药。

Cancer associated fibroblasts-derived SULF1 promotes gastric cancer metastasis and CDDP resistance through the TGFBR3-mediated TGF-β signaling pathway.

作者信息

Fang Xingchao, Chen Damin, Yang Xinyu, Cao Xiaogang, Cheng Quan, Liu Kanghui, Xu Peng, Wang Yanjuan, Xu Jiafeng, Zhao Siguo, Yan Zhengyuan

机构信息

Department of General Surgery, Nanjing Lishui People's Hospital, Nanjing, Jiangsu, China.

Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.

出版信息

Cell Death Discov. 2024 Mar 4;10(1):111. doi: 10.1038/s41420-024-01882-y.

DOI:10.1038/s41420-024-01882-y
PMID:38438372
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10912303/
Abstract

SULF1 has been implicated in a number of malignancies. The function of SULF1 in gastric cancer is disputed. The objective of this study was to examine the role and underlying molecular mechanisms of SULF1 in the context of gastric cancer. We found that the expression of SULF1 was increased in gastric cancer, especially in cancer-associated fibroblasts. The overexpression of SULF1 was found to be significantly correlated with unfavorable prognosis among individuals diagnosed with gastric cancer. Functionally, cancer-associated fibroblasts-derived SULF1 served as a oncogenic molecule which facilitated gastric cancer cells metastasis and CDDP resistance. Mechanistically, SULF1 regulated the communication between gastric cancer cells and cancer-associated fibroblasts in tumor microenvironment as a signaling molecule. Cancer-associated fibroblasts-secreted SULF1 interfered with the interaction between TGF-β1 and TGFBR3 by combining with TGFBR3 on gastric cancer cell membrane, subsequently activated TGF-β signaling pathway. In conclusion, our findings have presented novel approaches for potential treatment and prognosis prediction in individuals diagnosed with gastric cancer through the targeting of the CAFs-SULF1-TGFBR3-TGF-β1 signaling axis.

摘要

SULF1与多种恶性肿瘤有关。SULF1在胃癌中的功能存在争议。本研究的目的是探讨SULF1在胃癌中的作用及潜在分子机制。我们发现SULF1在胃癌中表达增加，尤其是在癌相关成纤维细胞中。在被诊断为胃癌的个体中，SULF1的过表达与不良预后显著相关。在功能上，癌相关成纤维细胞来源的SULF1作为一种致癌分子，促进胃癌细胞转移和对顺铂耐药。机制上，SULF1作为一种信号分子调节肿瘤微环境中胃癌细胞与癌相关成纤维细胞之间的通讯。癌相关成纤维细胞分泌的SULF1通过与胃癌细胞膜上的TGFBR3结合，干扰TGF-β1与TGFBR3之间的相互作用，随后激活TGF-β信号通路。总之，我们的研究结果通过靶向CAFs-SULF1-TGFBR3-TGF-β1信号轴，为诊断为胃癌的个体提供了潜在治疗和预后预测的新方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1526/10912303/e25e25773a15/41420_2024_1882_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1526/10912303/6bb7724861bf/41420_2024_1882_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1526/10912303/1588b35e57da/41420_2024_1882_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1526/10912303/e25e25773a15/41420_2024_1882_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1526/10912303/40739a39bc73/41420_2024_1882_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1526/10912303/3199f20078c2/41420_2024_1882_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1526/10912303/61325050ca34/41420_2024_1882_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1526/10912303/5500ec4d0899/41420_2024_1882_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1526/10912303/6bb7724861bf/41420_2024_1882_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1526/10912303/1588b35e57da/41420_2024_1882_Fig6_HTML.jpg
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