Metastasis remains a major challenge in the successful management of malignant diseases.The liver is a major site of metastatic disease and a leading cause of death from gastrointestinal malignancies such as colon,sto...Metastasis remains a major challenge in the successful management of malignant diseases.The liver is a major site of metastatic disease and a leading cause of death from gastrointestinal malignancies such as colon,stomach,and pancreatic cancers,as well as melanoma,breast cancer,and sarcoma.As an important factor that influences the development of metastatic liver cancer,alternative splicing drives the diversity of RNA transcripts and protein subtypes,which may provide potential to broaden the target space.In particular,the dysfunction of splicing factors and abnormal expression of splicing variants are associated with the occurrence,progression,aggressiveness,and drug resistance of cancers caused by the selective splicing of specific genes.This review is the first to provide a detailed summary of the normal splicing process and alterations that occur during metastatic liver cancer.It will cover the role of alternative splicing in the mechanisms of metastatic liver cancer by examining splicing factor changes,abnormal splicing,and the contribution of hypoxia to these changes during metastasis.展开更多
Cell-matrix interactions play a critical role in tissue repair and regeneration.With gradual uncovering of substrate mechanical characteristics that can affect cell-matrix interactions,much progress has been made to u...Cell-matrix interactions play a critical role in tissue repair and regeneration.With gradual uncovering of substrate mechanical characteristics that can affect cell-matrix interactions,much progress has been made to unravel substrate stiffness-mediated cellular response as well as its underlying mechanisms.Yet,as a part of cell-matrix interaction biology,this field remains in its infancy,and the detailed molecular mechanisms are still elusive regarding scaffold-modulated tissue regeneration.This review provides an overview of recent progress in the area of the substrate stiffness-mediated cellular responses,including 1)the physical determination of substrate stiffness on cell fate and tissue development;2)the current exploited approaches to manipulate the stiffness of scaffolds;3)the progress of recent researches to reveal the role of substrate stiffness in cellular responses in some representative tissue-engineered regeneration varying from stiff tissue to soft tissue.This article aims to provide an up-to-date overview of cell mechanobiology research in substrate stiffness mediated cellular response and tissue regeneration with insightful information to facilitate interdisciplinary knowledge transfer and enable the establishment of prognostic markers for the design of suitable biomaterials.展开更多
基金Supported by the National Natural Science Foundation of China,No.82002068,No.82272281the Natural Science Foundation of Guangdong Province,No.2021A1515010949.
文摘Metastasis remains a major challenge in the successful management of malignant diseases.The liver is a major site of metastatic disease and a leading cause of death from gastrointestinal malignancies such as colon,stomach,and pancreatic cancers,as well as melanoma,breast cancer,and sarcoma.As an important factor that influences the development of metastatic liver cancer,alternative splicing drives the diversity of RNA transcripts and protein subtypes,which may provide potential to broaden the target space.In particular,the dysfunction of splicing factors and abnormal expression of splicing variants are associated with the occurrence,progression,aggressiveness,and drug resistance of cancers caused by the selective splicing of specific genes.This review is the first to provide a detailed summary of the normal splicing process and alterations that occur during metastatic liver cancer.It will cover the role of alternative splicing in the mechanisms of metastatic liver cancer by examining splicing factor changes,abnormal splicing,and the contribution of hypoxia to these changes during metastasis.
基金supported by Fundamental Research Funds for National Key Research and Development Program of China(2018YFC1105800)China Postdoctoral Science Foundation(2020M681322)National Natural Science Foundation of China(31870967 and 81671921).
文摘Cell-matrix interactions play a critical role in tissue repair and regeneration.With gradual uncovering of substrate mechanical characteristics that can affect cell-matrix interactions,much progress has been made to unravel substrate stiffness-mediated cellular response as well as its underlying mechanisms.Yet,as a part of cell-matrix interaction biology,this field remains in its infancy,and the detailed molecular mechanisms are still elusive regarding scaffold-modulated tissue regeneration.This review provides an overview of recent progress in the area of the substrate stiffness-mediated cellular responses,including 1)the physical determination of substrate stiffness on cell fate and tissue development;2)the current exploited approaches to manipulate the stiffness of scaffolds;3)the progress of recent researches to reveal the role of substrate stiffness in cellular responses in some representative tissue-engineered regeneration varying from stiff tissue to soft tissue.This article aims to provide an up-to-date overview of cell mechanobiology research in substrate stiffness mediated cellular response and tissue regeneration with insightful information to facilitate interdisciplinary knowledge transfer and enable the establishment of prognostic markers for the design of suitable biomaterials.
