Wnt signaling transduces evolutionarily conserved pathways which play important roles in initiating and regulating a diverse range of cellular activities,including cell proliferation,calcium homeostasis,and cell polar...Wnt signaling transduces evolutionarily conserved pathways which play important roles in initiating and regulating a diverse range of cellular activities,including cell proliferation,calcium homeostasis,and cell polarity.The role of Wnt signaling in controlling cell proliferation and stem cell self-renewal is primarily carried out through the canonical pathway,which is the best-characterized the multiple Wnt signaling branches.The past 10 years has seen a rapid expansion in our understanding of the complexity of this pathway,as many new components of Wnt signaling have been identified and linked to signaling regulation,stem cell functions,and adult tissue homeostasis.Additionally,a substantial body of evidence links Wnt signaling to tumorigenesis of cancer types and implicates it in the development of cancer drug resistance.Thus,a better understanding of the mechanisms by which dysregulation of Wnt signaling precedes the development and progression of human cancer may hasten the development of pathway inhibitors to augment current therapy.This review summarizes and synthesizes our current knowledge of the canonical Wnt pathway in development and disease.We begin with an overview of the components of the canonical Wnt signaling pathway and delve into the role this pathway has been shown to play in stemness,tumorigenesis,and cancer drug resistance.Ultimately,we hope to present an organized collection of evidence implicating Wnt signaling in tumorigenesis and chemoresistance to facilitate the pursuit of Wnt pathway modulators that may improve outcomes of cancers in which Wnt signaling contributes to aggressive disease and/or treatment resistance.展开更多
Defects of articular cartilage present a unique clinical challenge due to its poor self-healing capacity and avascular nature.Current surgical treatment options do not ensure consistent regeneration of hyaline cartila...Defects of articular cartilage present a unique clinical challenge due to its poor self-healing capacity and avascular nature.Current surgical treatment options do not ensure consistent regeneration of hyaline cartilage in favor of fibrous tissue.Here,we review the current understanding of the most important biological regulators of chondrogenesis and their interactions,to provide insight into potential applications for cartilage tissue engineering.These include various signaling pathways,including fibroblast growth factors(FGFs),transforming growth factor b(TGF-b)/bone morphogenic proteins(BMPs),Wnt/b-catenin,Hedgehog,Notch,hypoxia,and angiogenic signaling pathways.Transcriptional and epigenetic regulation of chondrogenesis will also be discussed.Advances in our understanding of these signaling pathways have led to promising advances in cartilage regeneration and tissue engineering.展开更多
基金The authors’research efforts were supported in part by research grants from the NIH(AT004418 to TCH)the 973 Program of Ministry of Science and Technology(MOST)of China(#2011CB707900 to TCH)+1 种基金the Scoliosis Research Society(to MJL),MKM was a recipient of Howard Hughes Medical Institute Medical Research FellowshipCS was a recipient of the Pritzker Summer Research Fellowship funded through a NIH T-35 training grant(NIDDK).
文摘Wnt signaling transduces evolutionarily conserved pathways which play important roles in initiating and regulating a diverse range of cellular activities,including cell proliferation,calcium homeostasis,and cell polarity.The role of Wnt signaling in controlling cell proliferation and stem cell self-renewal is primarily carried out through the canonical pathway,which is the best-characterized the multiple Wnt signaling branches.The past 10 years has seen a rapid expansion in our understanding of the complexity of this pathway,as many new components of Wnt signaling have been identified and linked to signaling regulation,stem cell functions,and adult tissue homeostasis.Additionally,a substantial body of evidence links Wnt signaling to tumorigenesis of cancer types and implicates it in the development of cancer drug resistance.Thus,a better understanding of the mechanisms by which dysregulation of Wnt signaling precedes the development and progression of human cancer may hasten the development of pathway inhibitors to augment current therapy.This review summarizes and synthesizes our current knowledge of the canonical Wnt pathway in development and disease.We begin with an overview of the components of the canonical Wnt signaling pathway and delve into the role this pathway has been shown to play in stemness,tumorigenesis,and cancer drug resistance.Ultimately,we hope to present an organized collection of evidence implicating Wnt signaling in tumorigenesis and chemoresistance to facilitate the pursuit of Wnt pathway modulators that may improve outcomes of cancers in which Wnt signaling contributes to aggressive disease and/or treatment resistance.
基金The authors’ laboratories were supported in part byresearch grants from the National Institutes of Health(AR50142, AR054381, and AT004418 to RCH, HHL, and TCH)and Scoliosis Research Society (MJL)JDG and VT were recipientsof the Pritzker Summer Research Fellowship fundedthrough a NIH T-35 training grant (NIDDK)MKM was arecipient of Howard Hughes Medical Institute MedicalResearch Fellowship.
文摘Defects of articular cartilage present a unique clinical challenge due to its poor self-healing capacity and avascular nature.Current surgical treatment options do not ensure consistent regeneration of hyaline cartilage in favor of fibrous tissue.Here,we review the current understanding of the most important biological regulators of chondrogenesis and their interactions,to provide insight into potential applications for cartilage tissue engineering.These include various signaling pathways,including fibroblast growth factors(FGFs),transforming growth factor b(TGF-b)/bone morphogenic proteins(BMPs),Wnt/b-catenin,Hedgehog,Notch,hypoxia,and angiogenic signaling pathways.Transcriptional and epigenetic regulation of chondrogenesis will also be discussed.Advances in our understanding of these signaling pathways have led to promising advances in cartilage regeneration and tissue engineering.
