2. Academic Validation
  3. FOS-driven inflammatory CAFs promote colorectal cancer liver metastasis via the SFRP1-FGFR2-HIF1 axis

FOS-driven inflammatory CAFs promote colorectal cancer liver metastasis via the SFRP1-FGFR2-HIF1 axis

  • Theranostics. 2025 Mar 21;15(10):4593-4613. doi: 10.7150/thno.111625.
Long Liu 1 2,  Yuhao Ba 1 3 4,  Shuaixi Yang 5,  Aning Zuo 1 3 4,  Shutong Liu 1 3 4,  Yuyuan Zhang 1 3 4,  Shuqin Xu 2,  Siyuan Weng 1 6,  Benyu Liu 7,  Peng Luo 8,  Quan Cheng 9,  Jinhai Deng 10,  Hui Xu 1 3 4,  Yukang Chen 1 3 4,  Chuhan Zhang 11,  Xing Zhou 12,  Yuqing Ren 13,  Xinwei Han 1 3 4,  Zhenyu Hou 14,  Zaoqu Liu 1 3 4 15
Affiliations

Affiliations

  • 1 Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.
  • 2 Department of hepatobiliary surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi, 710061, China.
  • 3 Interventional Institute of Zhengzhou University, Zhengzhou, Henan, 450052, China.
  • 4 Interventional Treatment and Clinical Research Center of Henan Province, Zhengzhou, Henan, 450052, China.
  • 5 Department of Colorectal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, Henan, China.
  • 6 National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
  • 7 Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China.
  • 8 The Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
  • 9 Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • 10 Richard Dimbleby Department of Cancer Research, Comprehensive Cancer Centre, Kings College London, London, United Kingdom.
  • 11 Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.
  • 12 Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.
  • 13 Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.
  • 14 Department of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, China.
  • 15 Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
PMID: 40225580 DOI: 10.7150/thno.111625
Abstract

Rationale: Cancer-associated fibroblasts (CAFs) exhibit diverse functions, yet their roles in colorectal Cancer liver metastasis (CRLM) remain poorly understood. Methods: Through integrated analysis of single-cell RNA Sequencing and spatial transcriptomics from colorectal Cancer patients (CRCP: non-metastatic primary tumors; CRCM: metastatic primary tumors with liver metastases), combined with in vitro and in vivo models to investigate the role of CAFs in CRLM. In vitro experiments included six groups to reveal the role of SFRP1-producing CAFs, comprising PBS (control) and recombinant human SFRP1 (rhSFRP1) treated SW480 cells, PBS (control) and recombinant mouse SFRP1 (rmSFRP1) treated CT26 cells, and conditioned medium (CM) derived from CAF-NC and CAF-Sfrp1 treated CT26 cells. Preclinical models were further employed to elucidate the role of SFRP1 in CRLM. Subcutaneous xenografts models were constructed from PBS (control) and rhSFRP1 treated SW480 cells. For orthotopic tumor metastasis models, CT26 cells were pre-cultured with CAF-NC or CAF-Sfrp1 and then orthotopically injected into BALB/c mice. Results: We identified an inflammatory CAF subtype (CFD+ iCAFs) associated with poor clinical outcomes, advanced staging, and metastasis. Transcriptional regulation analysis revealed FOS-mediated differentiation of CFD+ iCAFs drives SFRP1 overexpression. In vitro and in vivo experiments confirmed that SFRP1-producing CAFs promote tumor stemness and epithelial-mesenchymal transition (EMT). Mechanistically, SFRP1 from CFD+ iCAFs binds FGFR2, activating the HIF1 signaling pathway to enhance tumor stemness, EMT, and CRLM progression. Conclusion: This study highlights CFD+ iCAFs as key regulators of tumor-stromal interactions and identifies SFRP1 as a potential therapeutic target in CRLM.

Keywords

Cancer-associated fibroblasts; Colorectal cancer liver metastasis; SFRP1; Single-cell RNA sequencing; Therapeutic target.

Figures
Products
Inhibitors & Agonists
Other Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z