Cancer-associated fibroblasts: multidimensional players in liver cancer

Cancer-associated fibroblasts (CAFs), the most abundant stromal cells in the tumor microenvironment (TME), control tumor growth through production and organization of the extracellular matrix (ECM) for a long time. However, the results from different studies that have focused on targeting CAFs to di...

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Main Authors: Yanyun Pan, Yuangang Qiu, Xinbin Zhou, Wei Mao, Xiaoming Xu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2025.1454546/full
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author Yanyun Pan
Yuangang Qiu
Xinbin Zhou
Wei Mao
Xiaoming Xu
author_facet Yanyun Pan
Yuangang Qiu
Xinbin Zhou
Wei Mao
Xiaoming Xu
author_sort Yanyun Pan
collection DOAJ
description Cancer-associated fibroblasts (CAFs), the most abundant stromal cells in the tumor microenvironment (TME), control tumor growth through production and organization of the extracellular matrix (ECM) for a long time. However, the results from different studies that have focused on targeting CAFs to disturb tumor progression are extremely controversial. Recent studies using advanced single-cell RNA sequencing technology (scRNAseq) combined with multiple genetically engineered mouse models have identified diverse CAF subpopulations in the premalignant liver microenvironment (PME) of hepatocellular carcinoma (HCC) and TME of intrahepatic cholangiocarcinoma (ICC), providing a deeper understanding of the exact roles of each CAF subpopulation in cancer development. This review focuses on the specific protein markers, signaling pathways, and functions of various emerging CAF subclusters that contribute to the development of ICC and HCC. Elucidating the role and regulation of CAF subpopulations under different pathophysiological conditions will facilitate the discovery of new therapeutics that modulate CAF activity.
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publisher Frontiers Media S.A.
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series Frontiers in Oncology
spelling doaj-art-7dfd2f2d94c14022a6ad099aeae679082025-08-20T03:07:21ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-04-011510.3389/fonc.2025.14545461454546Cancer-associated fibroblasts: multidimensional players in liver cancerYanyun Pan0Yuangang Qiu1Xinbin Zhou2Wei Mao3Xiaoming Xu4Department of Cardiology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, ChinaDepartment of Cardiology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, ChinaDepartment of Cardiology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, ChinaDepartment of Cardiology, Affiliated Zhejiang Hospital, Zhejiang University School of Medicine, Zhejiang Key Laboratory of Integrative Chinese and Western Medicine for Diagnosis and Treatment of Circulatory Diseases, Hangzhou, ChinaDepartment of Cardiology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, ChinaCancer-associated fibroblasts (CAFs), the most abundant stromal cells in the tumor microenvironment (TME), control tumor growth through production and organization of the extracellular matrix (ECM) for a long time. However, the results from different studies that have focused on targeting CAFs to disturb tumor progression are extremely controversial. Recent studies using advanced single-cell RNA sequencing technology (scRNAseq) combined with multiple genetically engineered mouse models have identified diverse CAF subpopulations in the premalignant liver microenvironment (PME) of hepatocellular carcinoma (HCC) and TME of intrahepatic cholangiocarcinoma (ICC), providing a deeper understanding of the exact roles of each CAF subpopulation in cancer development. This review focuses on the specific protein markers, signaling pathways, and functions of various emerging CAF subclusters that contribute to the development of ICC and HCC. Elucidating the role and regulation of CAF subpopulations under different pathophysiological conditions will facilitate the discovery of new therapeutics that modulate CAF activity.https://www.frontiersin.org/articles/10.3389/fonc.2025.1454546/fullcancer-associated fibroblastiCAFmyCAFhepatocellular carcinomaintrahepatic cholangiocarcinomatumor microenvironment
spellingShingle Yanyun Pan
Yuangang Qiu
Xinbin Zhou
Wei Mao
Xiaoming Xu
Cancer-associated fibroblasts: multidimensional players in liver cancer
Frontiers in Oncology
cancer-associated fibroblast
iCAF
myCAF
hepatocellular carcinoma
intrahepatic cholangiocarcinoma
tumor microenvironment
title Cancer-associated fibroblasts: multidimensional players in liver cancer
title_full Cancer-associated fibroblasts: multidimensional players in liver cancer
title_fullStr Cancer-associated fibroblasts: multidimensional players in liver cancer
title_full_unstemmed Cancer-associated fibroblasts: multidimensional players in liver cancer
title_short Cancer-associated fibroblasts: multidimensional players in liver cancer
title_sort cancer associated fibroblasts multidimensional players in liver cancer
topic cancer-associated fibroblast
iCAF
myCAF
hepatocellular carcinoma
intrahepatic cholangiocarcinoma
tumor microenvironment
url https://www.frontiersin.org/articles/10.3389/fonc.2025.1454546/full
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AT yuangangqiu cancerassociatedfibroblastsmultidimensionalplayersinlivercancer
AT xinbinzhou cancerassociatedfibroblastsmultidimensionalplayersinlivercancer
AT weimao cancerassociatedfibroblastsmultidimensionalplayersinlivercancer
AT xiaomingxu cancerassociatedfibroblastsmultidimensionalplayersinlivercancer