Background:Fibroblast activation protein(FAP),a cell surface serine protease,plays roles in tumor invasion and immune regulation.However,there is currently no pan-cancer analysis of FAP.Objective:We aimed to assess th...Background:Fibroblast activation protein(FAP),a cell surface serine protease,plays roles in tumor invasion and immune regulation.However,there is currently no pan-cancer analysis of FAP.Objective:We aimed to assess the pan-cancer expression profile of FAP,its molecular function,and its potential role in head and neck squamous cell carcinoma(HNSC).Methods:We analyzed gene expression,survival status,immune infiltration,and molecular functional pathways of FAP in The Cancer Genome Atlas(TCGA)and Genotype Tissue Expression(GTEx)tumors.Furthermore,to elucidate the role of FAP in HNSC,we performed proliferation,migration,and invasion assays post-FAP overexpression or knock-down.Results:FAP expression was elevated in nine tumor types and was associated with poor survival in eight of them.In the context of immune infiltration,FAP expression negatively correlated with CD8+T-cell infiltration infive tumor types and positively with regulatory T-cell infiltration in four tumor types.Our enrichment analysis highlighted FAP’s involvement in the PI3K-Akt signaling pathway.In HNSC cells,FAP overexpression activated the PI3K-Akt pathway,promoting tumor proliferation,migration,and invasion.Conversely,FAP knockdown showed inhibitory effects.Conclusion:Our study unveils the association of FAP with poor tumor prognosis across multiple cancers and highlights its potential as a therapeutic target in HNSC.展开更多
Salicylic acid(SA)plays an essential role in plant defense against biotrophic and semi-biotrophic pathogens.Following pathogen recognition,SA biosynthesis dramatically increases at the infection site of the host plant...Salicylic acid(SA)plays an essential role in plant defense against biotrophic and semi-biotrophic pathogens.Following pathogen recognition,SA biosynthesis dramatically increases at the infection site of the host plant.The manner in which pathogens sense and tolerate the onslaught of SA stress to survive in the plant following infection remains to be understood.The objective of this work was to determine how the model phytopathogen Xanthomonas campestris pv.campestris(Xcc)senses and effluxes SA during infection inside host plants.First,RNA-Seq analysis identified an SA-responsive operon Xcc4167-Xcc4171,encoding a MarR family transcription factor HepR and an RND(resistance-nodulation-cell division)family efflux pump HepABCD in Xcc.Electrophoretic mobility shift assays and DNase I footprint analysis revealed that HepR neg-atively regulated hepABCD expression by specifically binding to an AT-rich region of the promoter of the hepRABCD operon,Phep.Second,isothermal titration calorimetry and further genetic analysis suggest that HepR is a novel SA sensor.SA binding released HepR from its cognate promoter Pnep and then induced the expression of hepABCD.Third,the RND family efflux pump HepABCD was responsible for SA efflux.The hepRABCD cluster was also involved in the regulation of culture pH and quorum sensing signal diffusible signaling factor turnover.Finally,the hepRABCD cluster was transcribed during the XC1 infection of Chinese radish and was required for the full virulence of Xcc in Chinese radish and cabbage.These findings suggest that the ability of Xcc to co-opt the plant defense signal SA to activate the multidrug efflux pump may have evolved to ensure Xcc survival and virulence in susceptible host plants.展开更多
基金This study was supported in part by grants from the National Natural Science Foundation of China(No.82170972).
文摘Background:Fibroblast activation protein(FAP),a cell surface serine protease,plays roles in tumor invasion and immune regulation.However,there is currently no pan-cancer analysis of FAP.Objective:We aimed to assess the pan-cancer expression profile of FAP,its molecular function,and its potential role in head and neck squamous cell carcinoma(HNSC).Methods:We analyzed gene expression,survival status,immune infiltration,and molecular functional pathways of FAP in The Cancer Genome Atlas(TCGA)and Genotype Tissue Expression(GTEx)tumors.Furthermore,to elucidate the role of FAP in HNSC,we performed proliferation,migration,and invasion assays post-FAP overexpression or knock-down.Results:FAP expression was elevated in nine tumor types and was associated with poor survival in eight of them.In the context of immune infiltration,FAP expression negatively correlated with CD8+T-cell infiltration infive tumor types and positively with regulatory T-cell infiltration in four tumor types.Our enrichment analysis highlighted FAP’s involvement in the PI3K-Akt signaling pathway.In HNSC cells,FAP overexpression activated the PI3K-Akt pathway,promoting tumor proliferation,migration,and invasion.Conversely,FAP knockdown showed inhibitory effects.Conclusion:Our study unveils the association of FAP with poor tumor prognosis across multiple cancers and highlights its potential as a therapeutic target in HNSC.
基金This work was financially supported by research grants from the National Natural Science Foundation of China(Nos.31972231 and 32172355 to H.Y.W.).
文摘Salicylic acid(SA)plays an essential role in plant defense against biotrophic and semi-biotrophic pathogens.Following pathogen recognition,SA biosynthesis dramatically increases at the infection site of the host plant.The manner in which pathogens sense and tolerate the onslaught of SA stress to survive in the plant following infection remains to be understood.The objective of this work was to determine how the model phytopathogen Xanthomonas campestris pv.campestris(Xcc)senses and effluxes SA during infection inside host plants.First,RNA-Seq analysis identified an SA-responsive operon Xcc4167-Xcc4171,encoding a MarR family transcription factor HepR and an RND(resistance-nodulation-cell division)family efflux pump HepABCD in Xcc.Electrophoretic mobility shift assays and DNase I footprint analysis revealed that HepR neg-atively regulated hepABCD expression by specifically binding to an AT-rich region of the promoter of the hepRABCD operon,Phep.Second,isothermal titration calorimetry and further genetic analysis suggest that HepR is a novel SA sensor.SA binding released HepR from its cognate promoter Pnep and then induced the expression of hepABCD.Third,the RND family efflux pump HepABCD was responsible for SA efflux.The hepRABCD cluster was also involved in the regulation of culture pH and quorum sensing signal diffusible signaling factor turnover.Finally,the hepRABCD cluster was transcribed during the XC1 infection of Chinese radish and was required for the full virulence of Xcc in Chinese radish and cabbage.These findings suggest that the ability of Xcc to co-opt the plant defense signal SA to activate the multidrug efflux pump may have evolved to ensure Xcc survival and virulence in susceptible host plants.
