Insights into the mechanisms, regulation, and therapeutic implications of extracellular matrix stiffness in cancer

Abstract The tumor microenvironment (TME) is critical for cancer initiation, growth, metastasis, and therapeutic resistance. The extracellular matrix (ECM) is a significant tumor component that serves various functions, including mechanical support, TME regulation, and signal molecule generation. Th...

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Main Authors: Ximo Zhang, Abdullah Al‐Danakh, Xinqing Zhu, Dan Feng, Linlin Yang, Haotian Wu, Yingying Li, Shujing Wang, Qiwei Chen, Deyong Yang
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:Bioengineering & Translational Medicine
Subjects:
Online Access:https://doi.org/10.1002/btm2.10698
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author Ximo Zhang
Abdullah Al‐Danakh
Xinqing Zhu
Dan Feng
Linlin Yang
Haotian Wu
Yingying Li
Shujing Wang
Qiwei Chen
Deyong Yang
author_facet Ximo Zhang
Abdullah Al‐Danakh
Xinqing Zhu
Dan Feng
Linlin Yang
Haotian Wu
Yingying Li
Shujing Wang
Qiwei Chen
Deyong Yang
author_sort Ximo Zhang
collection DOAJ
description Abstract The tumor microenvironment (TME) is critical for cancer initiation, growth, metastasis, and therapeutic resistance. The extracellular matrix (ECM) is a significant tumor component that serves various functions, including mechanical support, TME regulation, and signal molecule generation. The quantity and cross‐linking status of ECM components are crucial factors in tumor development, as they determine tissue stiffness and the interaction between stiff TME and cancer cells, resulting in aberrant mechanotransduction, proliferation, migration, invasion, angiogenesis, immune evasion, and treatment resistance. Therefore, broad knowledge of ECM dysregulation in the TME might aid in developing innovative cancer therapies. This review summarized the available information on major ECM components, their functions, factors that increase and decrease matrix stiffness, and related signaling pathways that interplay between cancer cells and the ECM in TME. Moreover, mechanotransduction alters during tumorogenesis, and current drug therapy based on ECM as targets, as well as future efforts in ECM and cancer, are also discussed.
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issn 2380-6761
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publishDate 2025-01-01
publisher Wiley
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series Bioengineering & Translational Medicine
spelling doaj-art-afe35e7813d64ed4874aab92f53348262025-08-20T02:44:27ZengWileyBioengineering & Translational Medicine2380-67612025-01-01101n/an/a10.1002/btm2.10698Insights into the mechanisms, regulation, and therapeutic implications of extracellular matrix stiffness in cancerXimo Zhang0Abdullah Al‐Danakh1Xinqing Zhu2Dan Feng3Linlin Yang4Haotian Wu5Yingying Li6Shujing Wang7Qiwei Chen8Deyong Yang9Department of Urology First Affiliated Hospital of Dalian Medical University Dalian ChinaDepartment of Urology First Affiliated Hospital of Dalian Medical University Dalian ChinaDepartment of Urology First Affiliated Hospital of Dalian Medical University Dalian ChinaDepartment of Urology First Affiliated Hospital of Dalian Medical University Dalian ChinaDepartment of Urology First Affiliated Hospital of Dalian Medical University Dalian ChinaDepartment of Urology First Affiliated Hospital of Dalian Medical University Dalian ChinaDepartment of Discipline Construction Dalian Medical University Dalian ChinaDepartment of Biochemistry and Molecular Biology, Institute of Glycobiology Dalian Medical University Dalian ChinaDepartment of Urology First Affiliated Hospital of Dalian Medical University Dalian ChinaDepartment of Urology First Affiliated Hospital of Dalian Medical University Dalian ChinaAbstract The tumor microenvironment (TME) is critical for cancer initiation, growth, metastasis, and therapeutic resistance. The extracellular matrix (ECM) is a significant tumor component that serves various functions, including mechanical support, TME regulation, and signal molecule generation. The quantity and cross‐linking status of ECM components are crucial factors in tumor development, as they determine tissue stiffness and the interaction between stiff TME and cancer cells, resulting in aberrant mechanotransduction, proliferation, migration, invasion, angiogenesis, immune evasion, and treatment resistance. Therefore, broad knowledge of ECM dysregulation in the TME might aid in developing innovative cancer therapies. This review summarized the available information on major ECM components, their functions, factors that increase and decrease matrix stiffness, and related signaling pathways that interplay between cancer cells and the ECM in TME. Moreover, mechanotransduction alters during tumorogenesis, and current drug therapy based on ECM as targets, as well as future efforts in ECM and cancer, are also discussed.https://doi.org/10.1002/btm2.10698cancerECM stiffnessextracellular matrixsignaling pathwaystargeted therapytumor microenvironment
spellingShingle Ximo Zhang
Abdullah Al‐Danakh
Xinqing Zhu
Dan Feng
Linlin Yang
Haotian Wu
Yingying Li
Shujing Wang
Qiwei Chen
Deyong Yang
Insights into the mechanisms, regulation, and therapeutic implications of extracellular matrix stiffness in cancer
Bioengineering & Translational Medicine
cancer
ECM stiffness
extracellular matrix
signaling pathways
targeted therapy
tumor microenvironment
title Insights into the mechanisms, regulation, and therapeutic implications of extracellular matrix stiffness in cancer
title_full Insights into the mechanisms, regulation, and therapeutic implications of extracellular matrix stiffness in cancer
title_fullStr Insights into the mechanisms, regulation, and therapeutic implications of extracellular matrix stiffness in cancer
title_full_unstemmed Insights into the mechanisms, regulation, and therapeutic implications of extracellular matrix stiffness in cancer
title_short Insights into the mechanisms, regulation, and therapeutic implications of extracellular matrix stiffness in cancer
title_sort insights into the mechanisms regulation and therapeutic implications of extracellular matrix stiffness in cancer
topic cancer
ECM stiffness
extracellular matrix
signaling pathways
targeted therapy
tumor microenvironment
url https://doi.org/10.1002/btm2.10698
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