Epithelial-mesenchymal transition（EMT） and mesenchymal-epithelial transition（MET） are essential for embryonic development and also important in cancer progression. In a conventional model, epithelial-like cancer c...Epithelial-mesenchymal transition（EMT） and mesenchymal-epithelial transition（MET） are essential for embryonic development and also important in cancer progression. In a conventional model, epithelial-like cancer cells transit to mesenchymal-like tumor cells with great motility via EMT transcription factors; these mesenchymallike cells migrate through the circulation system, relocate to a suitable site and then convert back to an epithelial-like phenotype to regenerate the tumor. However, recent findings challenge this conventional model and support the existence of a stable hybrid epithelial/mesenchymal（E/M） tumor population. Hybrid E/M tumor cells exhibit both epithelial and mesenchymal properties, possess great metastatic and tumorigenic capacity and are associated with poorer patient prognosis. The hybrid E/M model and associated regulatory networks represent a conceptual change regarding tumor metastasis and organ colonization. It may lead to the development of novel treatment strategies to ultimately stop cancer progression and improve disease-free survival.展开更多
Glioblastoma(GBM)is a highly vascularized malignant brain tumor with poor clinical outcomes.Vasculogenic mimicry(VM)formed by aggressive GBM cells is an alternative approach for tumor blood supply and contributes to t...Glioblastoma(GBM)is a highly vascularized malignant brain tumor with poor clinical outcomes.Vasculogenic mimicry(VM)formed by aggressive GBM cells is an alternative approach for tumor blood supply and contributes to the failure of anti-angiogenic therapy.To date,there is still a lack of effective drugs that target VM formation in GBM.In the present study,we evaluated the effects of the plant cyclopeptide moroidin on VM formed by GBM cells and investigated its underlying molecular mechanisms.Moroidin significantly suppressed cell migration,tube formation,and the expression levels ofα-smooth muscle actin and matrix metalloproteinase-9 in human GBM cell lines at sublethal concentrations.The RNA sequencing data suggested the involvement of the epithelialmesenchymal transition(EMT)pathway in the mechanism of moroidin.Exposure to moroidin led to a concentration-dependent decrease in the expression levels of the EMT markers N-cadherin and vimentin in GBM cells.Moreover,moroidin significantly reduced the level of phosphorylated extracellular signal-regulated protein kinase(p-ERK)and inhibited the activation of β-catenin.Finally,we demonstrated that the plant cyclopeptide moroidin inhibited VM formation by GBM cells through inhibiting the ERK/β-catenin-mediated EMT.Therefore,our study indicates a potential application of moroidin as an anti-VM agent in the treatment of GBM.展开更多
Objective To investigate the expression of cyclin-dependent kinase 8(CDK8)in esophageal squamous cell carcinoma(ESCC)and its effect on ESCC cells,and to explore its potential molecular mechanism.Methods The expression...Objective To investigate the expression of cyclin-dependent kinase 8(CDK8)in esophageal squamous cell carcinoma(ESCC)and its effect on ESCC cells,and to explore its potential molecular mechanism.Methods The expression level of CDK8 mRNA was analyzed using UALCAN database,and then the expression level of CDK8 protein in tumor tissues of ESCC patients was detected by immunohistochemistry(IHC).Esophageal cancer cell lines Kyse-30 and Kyse-150 were stably transfected with lentivirus to achieve knockdown and overexpression of CDK8.EdU proliferation assay,cell colony formation assay,cell cycle assay,cell scratch assay and invasion assay were used to explore the effect of CDK8 protein expression level on the phenotype of ESCC cells.Subsequently,the effect of CDK8 on the growth of esophageal cancer xenografts in vitro was observed by subcutaneous tumor formation assay in mice.Finally,the expression of proliferation and metastasis related proteins was detected by Western blot.Results CDK8 showed high transcription and protein expression levels in ESCC tissues compared with normal esophageal tissues.Knockdown of CDK8 expression significantly inhibited the proliferation,migration and invasion of ESCC cells.In addition,inhibition of CDK8 expression significantly affected the JAK2/STAT3 pathway and the expression of E-cadherin/N-cadherin,while overexpression of CDK8 reversed these effects.Inhibition of STAT3 pathway reversed the promoting effect of CDK8 overexpression on ESCC cell phenotype.Conclusion CDK8 is a cancer-promoting factor of ESCC,which mediates the phosphorylation of JAK2/STAT3 and epithelial-mesenchymal transition(EMT).展开更多
目的:探究上皮细胞-间充质转化(EMT)标记物E-钙黏蛋白(E-cadherin)与波形蛋白(Vimentin)在胃癌淋巴结转移中的临床价值。方法:选择2021年2月至2023年8月荆门市妇幼保健院病理科接收的120例胃癌切除术患者病理组织样本,其中60例患者配有...目的:探究上皮细胞-间充质转化(EMT)标记物E-钙黏蛋白(E-cadherin)与波形蛋白(Vimentin)在胃癌淋巴结转移中的临床价值。方法:选择2021年2月至2023年8月荆门市妇幼保健院病理科接收的120例胃癌切除术患者病理组织样本,其中60例患者配有胃癌淋巴结转移组织,其余60例患者仅有胃癌原发病灶组织。采用免疫组织化学方法检测组织样本中E-cadherin和Vimentin蛋白的表达。采用SPSS for Windows 27.0软件进行资料的统计学分析。结果:胃癌原发病灶组织E-cadherin阳性率为38.33%(23/60),组化平均分为(1.38±0.74)分;胃癌转移淋巴结组织E-cadherin阳性率为53.33%(32/60),组化平均分为(2.43±0.16)分,对比差异显著(P<0.05)。胃癌原发病灶组织Vimentin阳性率为41.67%(25/60),组化平均分为(1.34±0.54)分;胃癌转移淋巴结组织Vimentin阳性率为60.00%(36/60),组化平均分为(2.52±0.75)分,对比差异显著(P<0.05)。淋巴结转移数目与E-cadherin、Vimentin阳性率及组化评分呈正相关(P<0.05)。结论:EMT标记物E-cadherin与Vimenitn与胃癌淋巴结转移紧密相关,可作为病情及治疗效果评估的重要标志物。展开更多
基金supported by operating grants from Canadian Breast Cancer Foundation-Ontario Regionthe Canadian Institutes of Health Research MOP111224 to LW
文摘Epithelial-mesenchymal transition（EMT） and mesenchymal-epithelial transition（MET） are essential for embryonic development and also important in cancer progression. In a conventional model, epithelial-like cancer cells transit to mesenchymal-like tumor cells with great motility via EMT transcription factors; these mesenchymallike cells migrate through the circulation system, relocate to a suitable site and then convert back to an epithelial-like phenotype to regenerate the tumor. However, recent findings challenge this conventional model and support the existence of a stable hybrid epithelial/mesenchymal（E/M） tumor population. Hybrid E/M tumor cells exhibit both epithelial and mesenchymal properties, possess great metastatic and tumorigenic capacity and are associated with poorer patient prognosis. The hybrid E/M model and associated regulatory networks represent a conceptual change regarding tumor metastasis and organ colonization. It may lead to the development of novel treatment strategies to ultimately stop cancer progression and improve disease-free survival.
基金This work was supported by the National Key Research and Development Program of China(Grant No.2022YFE0104800 to Feng Han)the National Natural Science Foundation of China(Grant No.82003764 to Lili Feng)the Project supported by the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(Grant No.19KJB350001 to Lili Feng).
文摘Glioblastoma(GBM)is a highly vascularized malignant brain tumor with poor clinical outcomes.Vasculogenic mimicry(VM)formed by aggressive GBM cells is an alternative approach for tumor blood supply and contributes to the failure of anti-angiogenic therapy.To date,there is still a lack of effective drugs that target VM formation in GBM.In the present study,we evaluated the effects of the plant cyclopeptide moroidin on VM formed by GBM cells and investigated its underlying molecular mechanisms.Moroidin significantly suppressed cell migration,tube formation,and the expression levels ofα-smooth muscle actin and matrix metalloproteinase-9 in human GBM cell lines at sublethal concentrations.The RNA sequencing data suggested the involvement of the epithelialmesenchymal transition(EMT)pathway in the mechanism of moroidin.Exposure to moroidin led to a concentration-dependent decrease in the expression levels of the EMT markers N-cadherin and vimentin in GBM cells.Moreover,moroidin significantly reduced the level of phosphorylated extracellular signal-regulated protein kinase(p-ERK)and inhibited the activation of β-catenin.Finally,we demonstrated that the plant cyclopeptide moroidin inhibited VM formation by GBM cells through inhibiting the ERK/β-catenin-mediated EMT.Therefore,our study indicates a potential application of moroidin as an anti-VM agent in the treatment of GBM.
文摘Objective To investigate the expression of cyclin-dependent kinase 8(CDK8)in esophageal squamous cell carcinoma(ESCC)and its effect on ESCC cells,and to explore its potential molecular mechanism.Methods The expression level of CDK8 mRNA was analyzed using UALCAN database,and then the expression level of CDK8 protein in tumor tissues of ESCC patients was detected by immunohistochemistry(IHC).Esophageal cancer cell lines Kyse-30 and Kyse-150 were stably transfected with lentivirus to achieve knockdown and overexpression of CDK8.EdU proliferation assay,cell colony formation assay,cell cycle assay,cell scratch assay and invasion assay were used to explore the effect of CDK8 protein expression level on the phenotype of ESCC cells.Subsequently,the effect of CDK8 on the growth of esophageal cancer xenografts in vitro was observed by subcutaneous tumor formation assay in mice.Finally,the expression of proliferation and metastasis related proteins was detected by Western blot.Results CDK8 showed high transcription and protein expression levels in ESCC tissues compared with normal esophageal tissues.Knockdown of CDK8 expression significantly inhibited the proliferation,migration and invasion of ESCC cells.In addition,inhibition of CDK8 expression significantly affected the JAK2/STAT3 pathway and the expression of E-cadherin/N-cadherin,while overexpression of CDK8 reversed these effects.Inhibition of STAT3 pathway reversed the promoting effect of CDK8 overexpression on ESCC cell phenotype.Conclusion CDK8 is a cancer-promoting factor of ESCC,which mediates the phosphorylation of JAK2/STAT3 and epithelial-mesenchymal transition(EMT).
文摘目的:探究上皮细胞-间充质转化(EMT)标记物E-钙黏蛋白(E-cadherin)与波形蛋白(Vimentin)在胃癌淋巴结转移中的临床价值。方法:选择2021年2月至2023年8月荆门市妇幼保健院病理科接收的120例胃癌切除术患者病理组织样本,其中60例患者配有胃癌淋巴结转移组织,其余60例患者仅有胃癌原发病灶组织。采用免疫组织化学方法检测组织样本中E-cadherin和Vimentin蛋白的表达。采用SPSS for Windows 27.0软件进行资料的统计学分析。结果:胃癌原发病灶组织E-cadherin阳性率为38.33%(23/60),组化平均分为(1.38±0.74)分;胃癌转移淋巴结组织E-cadherin阳性率为53.33%(32/60),组化平均分为(2.43±0.16)分,对比差异显著(P<0.05)。胃癌原发病灶组织Vimentin阳性率为41.67%(25/60),组化平均分为(1.34±0.54)分;胃癌转移淋巴结组织Vimentin阳性率为60.00%(36/60),组化平均分为(2.52±0.75)分,对比差异显著(P<0.05)。淋巴结转移数目与E-cadherin、Vimentin阳性率及组化评分呈正相关(P<0.05)。结论:EMT标记物E-cadherin与Vimenitn与胃癌淋巴结转移紧密相关,可作为病情及治疗效果评估的重要标志物。
