B-cell CLL/lymphoma 9(BCL9)is considered a key developmental regulator and a well-established oncogenic driver in multiple cancer types,mainly through potentiating the Wnt/β-catenin signaling.However,increasing evide...B-cell CLL/lymphoma 9(BCL9)is considered a key developmental regulator and a well-established oncogenic driver in multiple cancer types,mainly through potentiating the Wnt/β-catenin signaling.However,increasing evidences indicate that BCL9 also plays multiple Wnt-independent roles.Herein,we summarized the updates of the canonical and non-canonical functions of BCL9 in cellular,physiological,or pathological processes.Moreover,we also concluded that the targeted inhibitors disrupt the interaction ofβ-catenin with BCL9 reported recently.展开更多
Salmonella:mediated cancer therapy has achieved remarkable anti-tumor effects in experimental animal models,but the detailed mechanism remains unsolved.In this report,the active involvement of the host immune response...Salmonella:mediated cancer therapy has achieved remarkable anti-tumor effects in experimental animal models,but the detailed mechanism remains unsolved.In this report,the active involvement of the host immune response in this process was confirmed by comparing the tumor-suppressive effects of Salmonella in immunocompetent and immunodeficient mice bearing melanoma allografts.Since flagella are key inducers of the host immune response during bacterial infection,flagella were genetically disrupted to analyse their involvement in Salmonella-mediated cancer therapy.The results showed that flagellum-deficient strains failed to induce significant anti-tumor effects,even when more bacteria were administered to offset the difference in invasion efficiency.Flagella mainly activate immune cells via Flagellin/Toll-like receptor 5(TLR5)signalling pathway.Indeed,we showed that exogenous activation of TLR5 signalling by recombinant Flagellin and exogenous expression of TLR5 both enhanced the therapeutic efficacy of flagellum-deficient Salmonella against melanoma.Our study highlighted the therapeutic value of the interaction between Salmonella and the host immune response through Flagellin/TLR5 signalling pathway during Salmonella-mediated cancer therapy,thereby suggesting the potential application of TLR5 agonists in the cancer immune therapy.展开更多
基金supported by grants from the Zhejiang Provincial Natural Science Foundation of China(No.LR21H160001)"Pioneer"and"Leading Goose"R&DProgram of Zhejiang,China(No.2022C03004)+2 种基金the National Natural Science Foundation of China(No.82072646 to JC and No.82104214)Zhejiang Provincial Natural Science Foundation of China(No.LQ22H160016)Start-up Grant of Hangzhou Normal University(China)(No.4275C50222204072 to DH).
文摘B-cell CLL/lymphoma 9(BCL9)is considered a key developmental regulator and a well-established oncogenic driver in multiple cancer types,mainly through potentiating the Wnt/β-catenin signaling.However,increasing evidences indicate that BCL9 also plays multiple Wnt-independent roles.Herein,we summarized the updates of the canonical and non-canonical functions of BCL9 in cellular,physiological,or pathological processes.Moreover,we also concluded that the targeted inhibitors disrupt the interaction ofβ-catenin with BCL9 reported recently.
基金supported by grants from the Jiangsu Provincial Nature Science Foundation(BK20192005,China)National Natural Science Foundation of China(81630092,81903143,81802338,and 82072646)+1 种基金Zhejiang Provincial Natural Science Foundation of China for Distinguished Young Scholars(LR21H160001)Start-up Grant of HZNU(4125C5021820470,China)。
文摘Salmonella:mediated cancer therapy has achieved remarkable anti-tumor effects in experimental animal models,but the detailed mechanism remains unsolved.In this report,the active involvement of the host immune response in this process was confirmed by comparing the tumor-suppressive effects of Salmonella in immunocompetent and immunodeficient mice bearing melanoma allografts.Since flagella are key inducers of the host immune response during bacterial infection,flagella were genetically disrupted to analyse their involvement in Salmonella-mediated cancer therapy.The results showed that flagellum-deficient strains failed to induce significant anti-tumor effects,even when more bacteria were administered to offset the difference in invasion efficiency.Flagella mainly activate immune cells via Flagellin/Toll-like receptor 5(TLR5)signalling pathway.Indeed,we showed that exogenous activation of TLR5 signalling by recombinant Flagellin and exogenous expression of TLR5 both enhanced the therapeutic efficacy of flagellum-deficient Salmonella against melanoma.Our study highlighted the therapeutic value of the interaction between Salmonella and the host immune response through Flagellin/TLR5 signalling pathway during Salmonella-mediated cancer therapy,thereby suggesting the potential application of TLR5 agonists in the cancer immune therapy.
