The biological implications of matrix stiffness in the hallmarks of cancer
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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