The ability of cells to interact with extracellular matrix macromolecules is at the forefront of the regulation of cell phenotype and organization.Indeed most if not all cells bear specific cell surface receptors for ...The ability of cells to interact with extracellular matrix macromolecules is at the forefront of the regulation of cell phenotype and organization.Indeed most if not all cells bear specific cell surface receptors for these molecules,namely the integrins,which are specific for the ligation of various macromolecules such as the laminins,fibronectins and tenascins.It is now well established that integrins can regulate a variety of biological activities,most notably cell cycle and tissue-specific gene expression.In the intestine,several observations suggest functional roles for cell-matrix interactions in the regulation of epithelial cell functions.This article focuses on integrin α6β4 as a paradigm to illustrate the importance as well as the complexity of integrins in the mediation of cell-matrix interactions.Indeed,α6β4 has been well-characterized for its involvement as a link between the cytoskeleton and extracellular matrix molecules as well as in the activation of a variety of intracellular signalization processes in cooperation with growth factor receptors.Furthermore,recent studies show that distinct forms of α6 and β4 subunits are expressed in the human intestine and,more importantly,recent work provides experimental evidence that various forms of α6β4 can differentially regulate intestinal epithelial cell functions under both normal and pathological conditions.For instance,it has been discovered that colorectal cancer cells express a hybrid form of α6β4 that is never seen in normal cells.Although further work is needed,integrin α6β4 is emerging as a key regulator of intestinal functions in both intestinal health and disease.展开更多
As a major kind of cell surface adhesion molecules with signal transduction function,integrins play a major role in tumorigenesis and tumor progression.The role of integrins in tumor cells and the tumor microenvironme...As a major kind of cell surface adhesion molecules with signal transduction function,integrins play a major role in tumorigenesis and tumor progression.The role of integrins in tumor cells and the tumor microenvironment has been extensively revealed.Among the integrin family,integrinαvβ3 is the most studied integrin in the past 20 years.Plenty of preclinical and clinical studies have been conducted,which showed clinical benefits of targeting integrinαvβ3 in tumor imaging and treatment.Currently,the focus of interest is gradually shifting from integrinαvβ3 toward other integrin subtypes.Integrinα6 is expressed in many malignant tumors,such as colorectal cancer,head and neck squamous cell carcinoma,breast cancer,pancreatic cancer,and liver cancer,and its expression is correlated with poor survival of the patients.Recent studies have shown that tumor molecular imaging agents and therapeutic drugs targeting integrinα6 have excellent safety and efficacy in preclinical mouse models,encouraging clinical translation of this promising target.In this review,we briefly overview the physiological and pathological function of integrinα6 and highlight the recent advances in integrinα6-targeted imaging and therapeutics in tumors.展开更多
基金Supported by a Grant from the Canadian Institutes of Health Research MOP 97836
文摘The ability of cells to interact with extracellular matrix macromolecules is at the forefront of the regulation of cell phenotype and organization.Indeed most if not all cells bear specific cell surface receptors for these molecules,namely the integrins,which are specific for the ligation of various macromolecules such as the laminins,fibronectins and tenascins.It is now well established that integrins can regulate a variety of biological activities,most notably cell cycle and tissue-specific gene expression.In the intestine,several observations suggest functional roles for cell-matrix interactions in the regulation of epithelial cell functions.This article focuses on integrin α6β4 as a paradigm to illustrate the importance as well as the complexity of integrins in the mediation of cell-matrix interactions.Indeed,α6β4 has been well-characterized for its involvement as a link between the cytoskeleton and extracellular matrix molecules as well as in the activation of a variety of intracellular signalization processes in cooperation with growth factor receptors.Furthermore,recent studies show that distinct forms of α6 and β4 subunits are expressed in the human intestine and,more importantly,recent work provides experimental evidence that various forms of α6β4 can differentially regulate intestinal epithelial cell functions under both normal and pathological conditions.For instance,it has been discovered that colorectal cancer cells express a hybrid form of α6β4 that is never seen in normal cells.Although further work is needed,integrin α6β4 is emerging as a key regulator of intestinal functions in both intestinal health and disease.
基金National Natural Science Foundation of China(81972531)。
文摘As a major kind of cell surface adhesion molecules with signal transduction function,integrins play a major role in tumorigenesis and tumor progression.The role of integrins in tumor cells and the tumor microenvironment has been extensively revealed.Among the integrin family,integrinαvβ3 is the most studied integrin in the past 20 years.Plenty of preclinical and clinical studies have been conducted,which showed clinical benefits of targeting integrinαvβ3 in tumor imaging and treatment.Currently,the focus of interest is gradually shifting from integrinαvβ3 toward other integrin subtypes.Integrinα6 is expressed in many malignant tumors,such as colorectal cancer,head and neck squamous cell carcinoma,breast cancer,pancreatic cancer,and liver cancer,and its expression is correlated with poor survival of the patients.Recent studies have shown that tumor molecular imaging agents and therapeutic drugs targeting integrinα6 have excellent safety and efficacy in preclinical mouse models,encouraging clinical translation of this promising target.In this review,we briefly overview the physiological and pathological function of integrinα6 and highlight the recent advances in integrinα6-targeted imaging and therapeutics in tumors.
