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Abstract Tumor is the second leading cause of death worldwide and is one of the most concerned diseases in humanity. During the
occurrence and progression of malignant tumors tumor cells evolve a series of characteristics by the acquisition of genetic and
epigenetic alterations that enable them to survive and adapt to stress-related conditions in the tumor microenvironment TME . These
properties which are known as hallmarks of cancer include sustained proliferative signaling tumor metastasis angiogenesis
metabolic reprogramming resistance to cell death and promoting tumor inflammation. Recently the biological implications of
mechanical factors matrix stiffness fluid shear stress portal vein pressure etc. in TME have attracted increasing attention in
tumorigenesis and development. Matrix stiffness is a key physical factor of the tumor microenvironment as known as extracellular matrix
ECM stress. Studies have demonstrated that matrix stiffness in solid tumors increases significantly due to the collagen overproduction
pathological collagen crosslinking and fiber alignment in turn tumor cells sense this abnormal ECM stress and convert mechanical
signals into biochemical signals through their mechanical receptors and subsequently exacerbating cancer features. However the exact
mechanism of matrix stiffness in tumorigenesis and malignant transformation is not fully understood. This review summarizes the study
progress of ECM stiffness in regulating tumor characteristics and discusses the possibility of targeting ECM stiffness as a tumor
therapeutic strategy which provides new ideas for the development of matrix mechanic-based clinical tumor therapy.
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