Background:Curcumin is a plant polyphenol with antitumor properties and inhibits the development of colorectal cancer(CRC).However,as the molecular mechanism associated is still unclear,our study aimed to explore the ...Background:Curcumin is a plant polyphenol with antitumor properties and inhibits the development of colorectal cancer(CRC).However,as the molecular mechanism associated is still unclear,our study aimed to explore the underlying molecular mechanisms by which curcumin inhibits CRC.Methods:HT29 and SW480 cells were treated with curcumin or/and Doxycycline(DOX),and cell viability,colony forming ability,migration and invasion were confirmed by cell counting kit-8(CCK-8),colony forming,Transwell assays.And Yes-associated protein 1(YAP)and PDZ-binding motif(TAZ)signaling-related genes or proteins were analyzed using reverse transcription quantitative real-time PCR(RT-qPCR),western blot,and immunofluorescence assays.Then nude mice xenograft tumor model was constructed,YAP and Ki67 expressions were tested by immunohistochemistry(IHC)staining.Results:In our study,we proved that curcumin significantly inhibited the CRC cell viability,cell migration,and cell invasion abilities.In addition,curcumin inhibited YAP and Transcriptional coactivator with TAZ or the YAP/TAZ signaling axis in CRC cells.Further,in the nude mice model,curcumin treatment significantly decreased the size and weight of xenotransplant tumors.Conclusion:Therefore,curcumin significantly inhibited CRC development and invasion by regulating the YAP/TAZ signaling axis.展开更多
Objective:To explore the mechanism of Huatan Sanjie Fang(HTSJ)in regulating goiter in Graves'disease(GD)mice by detecting key factors of the Hippo signaling pathway.Methods:A mouse model of GD was established by i...Objective:To explore the mechanism of Huatan Sanjie Fang(HTSJ)in regulating goiter in Graves'disease(GD)mice by detecting key factors of the Hippo signaling pathway.Methods:A mouse model of GD was established by injecting Ad-TSHR289 adenovirus into the bilateral quadriceps femoris of female mice.Successful mouse models were then randomly divided into a model group,methimazole(MMI)group,and HTSJ group,and fed with deionized water,MMI(4.5 mg/kg per day),and HTSJ(35.10 g/kg per day),respectively,for 10 weeks.Histopathological changes of the thyroid gland were subsequently observed by hematoxylin-eosin staining.Radioimmunoassay was used to detect serum total thyroxine(T4)and thyrotrophin-receptor antibody(TRAb)levels.The relative expression of mRNA of Mst1,YAP,and TAZ were detected by quantitative real-time polymerase chain reaction,while the protein expression of Mst1,YAP,TAZ,pMst1,and pYAP were detected by western blot.Results:After 10 weeks of drug intervention,goiter and other pathological changes in the HTSJ group significantly improved compared with the model group,and the levels of serum T4 and TRAb significantly decreased(P=.002,P<.001,respectively).Decreased mRNA expression of Mst1,YAP,and TAZ,the key factors of the Hippo signaling transduction pathway,was also observed(P=.002,P=.022,P<.001,respectively).In contrast,protein expression of Mst1(P=.046),pMst1(P=.026),and p YAP(P=.004)increased,while protein expression of YAP and TAZ decreased(P=.041,P<.001,respectively).Conclusion:HTSJ can effectively improve goiter in GD mice through the Hippo signaling pathway.展开更多
The Yes-associated protein(YAP)is a downstream effector of the Hippo pathway and acts as a key transcription co-factor to regulate cell migration,proliferation,and survival.The Hippo pathway is evolutionarily conserve...The Yes-associated protein(YAP)is a downstream effector of the Hippo pathway and acts as a key transcription co-factor to regulate cell migration,proliferation,and survival.The Hippo pathway is evolutionarily conserved and controls tissue growth and organ size.Dysregulation and heterogeneity of this pathway are found in cancers,including oral squamous cell carcinoma(OSCC),leading to overexpression of YAP and its regulated proliferation machinery.The activity of YAP is associated with its nuclear expression and is negatively regulated by the Hippo kinase-mediated phosphorylation resulting in an induction of its cytoplasmic translocation.This review focuses on the role of YAP in OSCC in the context of cancer metastatic potential and highlights the latestfindings about the heterogeneity of YAP expression and its nuclear transcription activity in oral cancer cell lines.The review also discusses the potential target of YAP in oral cancer therapy and the recentfinding of the unprecedented role of the desmosomal cadherin desmoglein-3(DSG3)in regulating Hippo-YAP signaling.展开更多
基金This work was financially supported by the Second Batch of Medical and Health Science and Technology Plan(self-financing)Projects in Shantou in 2020,Shantou Science and Technology Bureau Document Shantou([2020]No.58).
文摘Background:Curcumin is a plant polyphenol with antitumor properties and inhibits the development of colorectal cancer(CRC).However,as the molecular mechanism associated is still unclear,our study aimed to explore the underlying molecular mechanisms by which curcumin inhibits CRC.Methods:HT29 and SW480 cells were treated with curcumin or/and Doxycycline(DOX),and cell viability,colony forming ability,migration and invasion were confirmed by cell counting kit-8(CCK-8),colony forming,Transwell assays.And Yes-associated protein 1(YAP)and PDZ-binding motif(TAZ)signaling-related genes or proteins were analyzed using reverse transcription quantitative real-time PCR(RT-qPCR),western blot,and immunofluorescence assays.Then nude mice xenograft tumor model was constructed,YAP and Ki67 expressions were tested by immunohistochemistry(IHC)staining.Results:In our study,we proved that curcumin significantly inhibited the CRC cell viability,cell migration,and cell invasion abilities.In addition,curcumin inhibited YAP and Transcriptional coactivator with TAZ or the YAP/TAZ signaling axis in CRC cells.Further,in the nude mice model,curcumin treatment significantly decreased the size and weight of xenotransplant tumors.Conclusion:Therefore,curcumin significantly inhibited CRC development and invasion by regulating the YAP/TAZ signaling axis.
基金supported by the National Natural Science Fund(82004337)the Beijing University of Chinese Medicine new teacher launch fund(2020-JYB-XJSJJ-002)。
文摘Objective:To explore the mechanism of Huatan Sanjie Fang(HTSJ)in regulating goiter in Graves'disease(GD)mice by detecting key factors of the Hippo signaling pathway.Methods:A mouse model of GD was established by injecting Ad-TSHR289 adenovirus into the bilateral quadriceps femoris of female mice.Successful mouse models were then randomly divided into a model group,methimazole(MMI)group,and HTSJ group,and fed with deionized water,MMI(4.5 mg/kg per day),and HTSJ(35.10 g/kg per day),respectively,for 10 weeks.Histopathological changes of the thyroid gland were subsequently observed by hematoxylin-eosin staining.Radioimmunoassay was used to detect serum total thyroxine(T4)and thyrotrophin-receptor antibody(TRAb)levels.The relative expression of mRNA of Mst1,YAP,and TAZ were detected by quantitative real-time polymerase chain reaction,while the protein expression of Mst1,YAP,TAZ,pMst1,and pYAP were detected by western blot.Results:After 10 weeks of drug intervention,goiter and other pathological changes in the HTSJ group significantly improved compared with the model group,and the levels of serum T4 and TRAb significantly decreased(P=.002,P<.001,respectively).Decreased mRNA expression of Mst1,YAP,and TAZ,the key factors of the Hippo signaling transduction pathway,was also observed(P=.002,P=.022,P<.001,respectively).In contrast,protein expression of Mst1(P=.046),pMst1(P=.026),and p YAP(P=.004)increased,while protein expression of YAP and TAZ decreased(P=.041,P<.001,respectively).Conclusion:HTSJ can effectively improve goiter in GD mice through the Hippo signaling pathway.
文摘为了考察中药制剂西黄丸(Xihuang Pill)对肝癌细胞的作用及对Yes相关蛋白/具有PDZ结合基序的转录共激活因子(Yes-associated protein/transcriptional co-activator with PDZ-binding motif,YAP/TAZ)信号通路的影响,在SD大鼠中利用灌胃给药和动脉采血技术,制备西黄丸含药血清;利用磺酰罗丹明B(sulforhodamine B,SRB)染色技术,检测西黄丸含药血清对肝癌细胞增殖能力和克隆形成能力的影响;利用流式细胞术和原位末端转移酶标记(terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling,TUNEL)技术,检测西黄丸含药血清对肝癌细胞凋亡的影响;利用小室迁移测定实验模型,检测西黄丸含药血清对肝癌细胞侵袭和迁移能力的影响;利用小鼠肿瘤细胞异种移植模型,检测西黄丸对肝癌细胞体内增殖能力的影响;利用蛋白质印迹技术和荧光定量PCR技术,检测西黄丸含药血清对YAP/TAZ信号通路相关蛋白质和基因表达的影响。体外结果显示,西黄丸含药血清显著抑制肝癌细胞的体外增殖、克隆形成、侵袭和迁移能力,显著促进肝癌细胞的凋亡,显著抑制YAP/TAZ信号通路相关蛋白质和基因的表达,且具有剂量依赖性。体内结果显示,西黄丸显著抑制肝癌细胞的体内增殖能力,且具有剂量依赖性。研究结果提示,西黄丸能抑制肝癌细胞的体内外增殖、侵袭和转移能力,并可能在YAP/TAZ信号通路中发挥作用。
基金founded by Elfarouq Foundation(a small charity).
文摘The Yes-associated protein(YAP)is a downstream effector of the Hippo pathway and acts as a key transcription co-factor to regulate cell migration,proliferation,and survival.The Hippo pathway is evolutionarily conserved and controls tissue growth and organ size.Dysregulation and heterogeneity of this pathway are found in cancers,including oral squamous cell carcinoma(OSCC),leading to overexpression of YAP and its regulated proliferation machinery.The activity of YAP is associated with its nuclear expression and is negatively regulated by the Hippo kinase-mediated phosphorylation resulting in an induction of its cytoplasmic translocation.This review focuses on the role of YAP in OSCC in the context of cancer metastatic potential and highlights the latestfindings about the heterogeneity of YAP expression and its nuclear transcription activity in oral cancer cell lines.The review also discusses the potential target of YAP in oral cancer therapy and the recentfinding of the unprecedented role of the desmosomal cadherin desmoglein-3(DSG3)in regulating Hippo-YAP signaling.
