Introduction:Sulfatase 2(SULF2),an endogenous extracellular sulfatase,can remove 6-O-sulfate groups of glucosamine residues from heparan sulfate(HS)chains to modulate the Wnt/β-catenin signaling pathway,which plays a...Introduction:Sulfatase 2(SULF2),an endogenous extracellular sulfatase,can remove 6-O-sulfate groups of glucosamine residues from heparan sulfate(HS)chains to modulate the Wnt/β-catenin signaling pathway,which plays an important role in both liver carcinogenesis and embryogenesis.Side population(SP)cells are widely identified as stem-like cancer cells and are closely related to carcinoma metastasis,recurrence,and poor patient prognosis.However,the roles of SULF2 in SP cells of hepatomas are unclear,and the underlying mechanism is undefined.Objectives:This study aimed to compare the heterogeneity between SP cells and non-side population(NSP)cells derived from three different liver cancer cell lines and to elucidate the involvement of the SULF2-Wnt/β-catenin axis in liver cancer stem cells(CSCs)and its impact on the processes of carcinogenesis and invasiveness.Methods:In this work,three different liver cancer SP cells(HepG2,Huh7,and PRC/PRL/5)were sorted by flow cytometry.We also examined the migration and invasion behaviors of SP and NSP cells.To determine if this high tumorigenic potential of SP cells is correlated to SULF2,qPCR,western blotting,and immunofluorescence analysis were conducted.We also performed nude mouse xenograft experiments for in vivo analysis.Results:The results from the in vitro colony formation assay showed that SP cells exhibited a 2-fold higher colony formation efficiency compared to their NSP counterparts.The SP cells exhibited significantly higher potentials in terms of their migratory capacity and invasive ability compared to NSP cells.We found that higher expression of SULF2 in SP cells was associated with greater capabilities for clonogenicity,migration,and invasion.It was also linked to higher activation of the Wnt/β-catenin signaling pathway via stimulation of key downstream factors,particularlyβ-catenin,c-Myc,and cyclin D1.Further,a positive correlation between the upregulated SULF2 expression and tumorigenesis in the in vivo nude mouse xenograft models was demonstrated,highlighting that the potential underlying mechanism was Wnt/β-catenin signaling pathway activation.Conclusion:Our findings show that variable SULF2 expression was associated with differential activation of the Wnt/β-catenin signaling pathway,which could lead to behavioral differences between SP and NSP cells and also among the SP cells of the three liver cancer cell lines assessed.It was reasonably concluded that the SULF2-Wnt/β-catenin axis could play an important role in the tumorigenicity of liver cancer stem cells.展开更多
An occasional presence of bivalent stimuli in a block of univalent trials can elicit a slowing of the response on all subsequent univalent trials.This type of modulation of cognitive control is termed the bivalency ef...An occasional presence of bivalent stimuli in a block of univalent trials can elicit a slowing of the response on all subsequent univalent trials.This type of modulation of cognitive control is termed the bivalency effect.To explore whether this modulation is task specific,this study used a triplet task switching paradigm,with three following tasks that were presented concussively:a shape color judgment(red vs.blue),a number parity judgment(odd vs.even),and a letter case judgment(lowercase vs.upper-case).The event-related potential(ERP)results showed that(1)the bivalency effect was reflected by the decreased amplitude of N2 and P3a over the frontal region for both the color and letter tasks;(2)the bivalency effect occurred earlier for the color task compared with that for the letter task;(3)for the number parity task,the bivalency effect was observed in the increased N1 and the decreased P2p over the parietal region.These findings indicate that the modulation of cognitive control is task-specific after the presentation of bivalent stimuli in task switching.展开更多
基金supported by the Shenzhen Science and Technology Innovation Commission Fundamental Research Key Projects(Nos.JCYJ20180508153013853,JCYJ20180508152130899)the Shenzhen Science and Technology Innovation Fund(No.JCYJ20150331142757381)the National Natural Science Foundation of China(Nos.81641051,81872368).
文摘Introduction:Sulfatase 2(SULF2),an endogenous extracellular sulfatase,can remove 6-O-sulfate groups of glucosamine residues from heparan sulfate(HS)chains to modulate the Wnt/β-catenin signaling pathway,which plays an important role in both liver carcinogenesis and embryogenesis.Side population(SP)cells are widely identified as stem-like cancer cells and are closely related to carcinoma metastasis,recurrence,and poor patient prognosis.However,the roles of SULF2 in SP cells of hepatomas are unclear,and the underlying mechanism is undefined.Objectives:This study aimed to compare the heterogeneity between SP cells and non-side population(NSP)cells derived from three different liver cancer cell lines and to elucidate the involvement of the SULF2-Wnt/β-catenin axis in liver cancer stem cells(CSCs)and its impact on the processes of carcinogenesis and invasiveness.Methods:In this work,three different liver cancer SP cells(HepG2,Huh7,and PRC/PRL/5)were sorted by flow cytometry.We also examined the migration and invasion behaviors of SP and NSP cells.To determine if this high tumorigenic potential of SP cells is correlated to SULF2,qPCR,western blotting,and immunofluorescence analysis were conducted.We also performed nude mouse xenograft experiments for in vivo analysis.Results:The results from the in vitro colony formation assay showed that SP cells exhibited a 2-fold higher colony formation efficiency compared to their NSP counterparts.The SP cells exhibited significantly higher potentials in terms of their migratory capacity and invasive ability compared to NSP cells.We found that higher expression of SULF2 in SP cells was associated with greater capabilities for clonogenicity,migration,and invasion.It was also linked to higher activation of the Wnt/β-catenin signaling pathway via stimulation of key downstream factors,particularlyβ-catenin,c-Myc,and cyclin D1.Further,a positive correlation between the upregulated SULF2 expression and tumorigenesis in the in vivo nude mouse xenograft models was demonstrated,highlighting that the potential underlying mechanism was Wnt/β-catenin signaling pathway activation.Conclusion:Our findings show that variable SULF2 expression was associated with differential activation of the Wnt/β-catenin signaling pathway,which could lead to behavioral differences between SP and NSP cells and also among the SP cells of the three liver cancer cell lines assessed.It was reasonably concluded that the SULF2-Wnt/β-catenin axis could play an important role in the tumorigenicity of liver cancer stem cells.
基金supported by the National Natural Science Foundation of China(Grant Nos.32360201,31860278 and 31760285).
文摘An occasional presence of bivalent stimuli in a block of univalent trials can elicit a slowing of the response on all subsequent univalent trials.This type of modulation of cognitive control is termed the bivalency effect.To explore whether this modulation is task specific,this study used a triplet task switching paradigm,with three following tasks that were presented concussively:a shape color judgment(red vs.blue),a number parity judgment(odd vs.even),and a letter case judgment(lowercase vs.upper-case).The event-related potential(ERP)results showed that(1)the bivalency effect was reflected by the decreased amplitude of N2 and P3a over the frontal region for both the color and letter tasks;(2)the bivalency effect occurred earlier for the color task compared with that for the letter task;(3)for the number parity task,the bivalency effect was observed in the increased N1 and the decreased P2p over the parietal region.These findings indicate that the modulation of cognitive control is task-specific after the presentation of bivalent stimuli in task switching.
