Dynamic and heterogeneous interaction between tumor cells and the surrounding microenvironment fuels the occurrence,progression,invasion,and metastasis of solid tumors.In this process,the tumormicroenvironment(TME)fra...Dynamic and heterogeneous interaction between tumor cells and the surrounding microenvironment fuels the occurrence,progression,invasion,and metastasis of solid tumors.In this process,the tumormicroenvironment(TME)fractures cellular and matrix architecture normality through biochemical and mechanical means,abetting tumorigenesis and treatment resistance.Tumor cells sense and respond to the strength,direction,and duration of mechanical cues in the TME by various mechanotransduction pathways.However,far less understood is the comprehensive perspective of the functions and mechanisms of mechanotransduction.Due to the great therapeutic difficulties brought by the mechanical changes in the TME,emerging studies have focused on targeting the adverse mechanical factors in the TME to attenuate disease rather than conventionally targeting tumor cells themselves,which has been proven to be a potential therapeutic approach.In this review,we discussed the origins and roles ofmechanical factors in the TME,cell sensing,mechano-biological coupling and signal transduction,in vitro construction of the tumormechanicalmicroenvironment,applications and clinical significance in the TME.展开更多
Breast cancerhas been one of the biggest killers of women due to its susceptibility and high metastasis.Pathological observations show that malignant cancer cells frequently invade the surrounding normal tissue in col...Breast cancerhas been one of the biggest killers of women due to its susceptibility and high metastasis.Pathological observations show that malignant cancer cells frequently invade the surrounding normal tissue in collective rather than individual cell migration.1,2 For individual cell migration,it has been found that the Rho/ROCK signaling is upregulated and correlates with disease progression.3 Meanwhile,Rho activates myosin-ll and the actomyosin-mediated contraction creates tension within the cells.4,5 However,the roles of the activation of the Rho/RoCK signal pathway in collective cell migration and the precise mechanisms by which myosin-ll fine-tunes the contractility of the cells to allow for the reorganization of the cytoskeleton that drives collective cell migration,remain unclear.This study investigated whether the high cellular contractility could activate the inside-out signal transductions and how did the intracellular force contribute to the collective cell migration.展开更多
基金National Natural Science Foundation of China,Grant/Award Numbers:U19A2006,12132004,11972111,31900940,32071304,32171309,32171395Sichuan Science and Technology Program,Grant/Award Number:21YJ0130Joint Funds of Center for Engineering Medicine,Grant/Award Numbers:ZYGX2021YGLH017,ZYGX2021YGLH010,ZYGX2021YGLH023。
文摘Dynamic and heterogeneous interaction between tumor cells and the surrounding microenvironment fuels the occurrence,progression,invasion,and metastasis of solid tumors.In this process,the tumormicroenvironment(TME)fractures cellular and matrix architecture normality through biochemical and mechanical means,abetting tumorigenesis and treatment resistance.Tumor cells sense and respond to the strength,direction,and duration of mechanical cues in the TME by various mechanotransduction pathways.However,far less understood is the comprehensive perspective of the functions and mechanisms of mechanotransduction.Due to the great therapeutic difficulties brought by the mechanical changes in the TME,emerging studies have focused on targeting the adverse mechanical factors in the TME to attenuate disease rather than conventionally targeting tumor cells themselves,which has been proven to be a potential therapeutic approach.In this review,we discussed the origins and roles ofmechanical factors in the TME,cell sensing,mechano-biological coupling and signal transduction,in vitro construction of the tumormechanicalmicroenvironment,applications and clinical significance in the TME.
基金supported,in part or in whole,by the National Natural Science Foundation of China(No.32071304,U19A2006,12132004,11972111,and 32171309)the China Postdoctoral Science Foundation(No.2019T120821)+1 种基金the Natural Science Foundation of Sichuan Program(No.23NSFSC3552,2022NSFSC0048,2022NSFSC0686,23SYSX0108,and 2023NSFSC1233)the Joint Funds of Center for Engineering Medicine(No.ZYGX2021YGLH017).
文摘Breast cancerhas been one of the biggest killers of women due to its susceptibility and high metastasis.Pathological observations show that malignant cancer cells frequently invade the surrounding normal tissue in collective rather than individual cell migration.1,2 For individual cell migration,it has been found that the Rho/ROCK signaling is upregulated and correlates with disease progression.3 Meanwhile,Rho activates myosin-ll and the actomyosin-mediated contraction creates tension within the cells.4,5 However,the roles of the activation of the Rho/RoCK signal pathway in collective cell migration and the precise mechanisms by which myosin-ll fine-tunes the contractility of the cells to allow for the reorganization of the cytoskeleton that drives collective cell migration,remain unclear.This study investigated whether the high cellular contractility could activate the inside-out signal transductions and how did the intracellular force contribute to the collective cell migration.
