Cancer stem cells(CSCs)are widely acknowledged as primary mediators to the initiation and progression of tumors.The association between microbial infection and cancer stemness has garnered considerable scholarly inter...Cancer stem cells(CSCs)are widely acknowledged as primary mediators to the initiation and progression of tumors.The association between microbial infection and cancer stemness has garnered considerable scholarly interest in recent years.Porphyromonas gingivalis(P.gingivalis)is increasingly considered to be closely related to the development of oral squamous cell carcinoma(OSCC).Nevertheless,the role of P.gingivalis in the stemness of OSCC cells remains uncertain.Herein,we showed that P.gingivalis was positively correlated with CSC markers expression in human OSCC specimens,promoted the stemness and tumorigenicity of OSCC cells,and enhanced tumor formation in nude mice.Mechanistically,P.gingivalis increased lipid synthesis in OSCC cells by upregulating the expression of stearoyl-CoA desaturase 1(SCD1)expression,a key enzyme involved in lipid metabolism,which ultimately resulted in enhanced acquisition of stemness.Moreover,SCD1 suppression attenuated P.gingivalis-induced stemness of OSCC cells,including CSCs markers expression,sphere formation ability,chemoresistance,and tumor growth,in OSCC cells both in vitro and in vivo.Additionally,upregulation of SCD1 in P.gingivalis-infected OSCC cells was associated with the expression of KLF5,and that was modulated by P.gingivalis-activated NOD1 signaling.Taken together,these findings highlight the importance of SCD1-dependent lipid synthesis in P.gingivalis-induced stemness acquisition in OSCC cells,suggest that the NOD1/KLF5 axis may play a key role in regulating SCD1 expression and provide a molecular basis for targeting SCD1 as a new option for attenuating OSCC cells stemness.展开更多
为了解旋毛虫ES抗原对宿主巨噬细胞NOD1受体通路的影响,本研究通过体外实验将旋毛虫ES抗原作用于小鼠腹腔巨噬细胞,观察NOD1受体及其信号通路中关键分子及相关细胞因子的表达动态。应用荧光定量PCR监测细胞内NOD1、RIP2和NF-κB m RNA...为了解旋毛虫ES抗原对宿主巨噬细胞NOD1受体通路的影响,本研究通过体外实验将旋毛虫ES抗原作用于小鼠腹腔巨噬细胞,观察NOD1受体及其信号通路中关键分子及相关细胞因子的表达动态。应用荧光定量PCR监测细胞内NOD1、RIP2和NF-κB m RNA的转录水平,western blot测定NOD1、RIP2、NF-κBp65、NF-κB p-p65蛋白表达量,ELISA测定细胞培养上清中TNF-α、IL-1β和IL-6含量变化。结果显示,在一定的ES抗原作用浓度和时间范围内,巨噬细胞中各目的基因的转录水平均先增高,当作用时间和作用浓度超过一定值时则开始下降,作用24 h时NOD1 m RNA转录水平显著低于对照组(p<0.01);ES抗原浓度15μg/mL作用时间9 h时,巨噬细胞中NOD1、RIP2和NF-κB p-p65蛋白量显著增加(p<0.01),此时巨噬细胞培养上清中TNF-α、IL-1β、IL-6含量显著增高(p<0.01)。结果表明,旋毛虫ES抗原在一定的作用时间和浓度范围内,可以激活并调节小鼠腹腔巨噬细胞中NOD1受体通路,上调NOD1受体通路中关键分子RIP2和下游分子NF-κB的表达,可以促进细胞因子TNF-α、IL-1β和IL-6的分泌;并且超过一定时间和浓度的ES抗原刺激可以导致小鼠腹腔巨噬细胞出现免疫耐受。本研究证明了宿主NOD1受体参与了旋毛虫引起的宿主免疫应答,为旋毛虫病防治和理解旋毛虫对宿主的感染机制提供新的思路。展开更多
基金supported by the National Natural Science Foundation of China(grant#82370975 and 82170969)。
文摘Cancer stem cells(CSCs)are widely acknowledged as primary mediators to the initiation and progression of tumors.The association between microbial infection and cancer stemness has garnered considerable scholarly interest in recent years.Porphyromonas gingivalis(P.gingivalis)is increasingly considered to be closely related to the development of oral squamous cell carcinoma(OSCC).Nevertheless,the role of P.gingivalis in the stemness of OSCC cells remains uncertain.Herein,we showed that P.gingivalis was positively correlated with CSC markers expression in human OSCC specimens,promoted the stemness and tumorigenicity of OSCC cells,and enhanced tumor formation in nude mice.Mechanistically,P.gingivalis increased lipid synthesis in OSCC cells by upregulating the expression of stearoyl-CoA desaturase 1(SCD1)expression,a key enzyme involved in lipid metabolism,which ultimately resulted in enhanced acquisition of stemness.Moreover,SCD1 suppression attenuated P.gingivalis-induced stemness of OSCC cells,including CSCs markers expression,sphere formation ability,chemoresistance,and tumor growth,in OSCC cells both in vitro and in vivo.Additionally,upregulation of SCD1 in P.gingivalis-infected OSCC cells was associated with the expression of KLF5,and that was modulated by P.gingivalis-activated NOD1 signaling.Taken together,these findings highlight the importance of SCD1-dependent lipid synthesis in P.gingivalis-induced stemness acquisition in OSCC cells,suggest that the NOD1/KLF5 axis may play a key role in regulating SCD1 expression and provide a molecular basis for targeting SCD1 as a new option for attenuating OSCC cells stemness.
文摘为了解旋毛虫ES抗原对宿主巨噬细胞NOD1受体通路的影响,本研究通过体外实验将旋毛虫ES抗原作用于小鼠腹腔巨噬细胞,观察NOD1受体及其信号通路中关键分子及相关细胞因子的表达动态。应用荧光定量PCR监测细胞内NOD1、RIP2和NF-κB m RNA的转录水平,western blot测定NOD1、RIP2、NF-κBp65、NF-κB p-p65蛋白表达量,ELISA测定细胞培养上清中TNF-α、IL-1β和IL-6含量变化。结果显示,在一定的ES抗原作用浓度和时间范围内,巨噬细胞中各目的基因的转录水平均先增高,当作用时间和作用浓度超过一定值时则开始下降,作用24 h时NOD1 m RNA转录水平显著低于对照组(p<0.01);ES抗原浓度15μg/mL作用时间9 h时,巨噬细胞中NOD1、RIP2和NF-κB p-p65蛋白量显著增加(p<0.01),此时巨噬细胞培养上清中TNF-α、IL-1β、IL-6含量显著增高(p<0.01)。结果表明,旋毛虫ES抗原在一定的作用时间和浓度范围内,可以激活并调节小鼠腹腔巨噬细胞中NOD1受体通路,上调NOD1受体通路中关键分子RIP2和下游分子NF-κB的表达,可以促进细胞因子TNF-α、IL-1β和IL-6的分泌;并且超过一定时间和浓度的ES抗原刺激可以导致小鼠腹腔巨噬细胞出现免疫耐受。本研究证明了宿主NOD1受体参与了旋毛虫引起的宿主免疫应答,为旋毛虫病防治和理解旋毛虫对宿主的感染机制提供新的思路。
