Epithelial–mesenchymal transition(EMT)is involved in both physiological and pathological processes.EMT plays an essential role in the invasion,migration and metastasis of tumours.Autophagy has been shown to regulate ...Epithelial–mesenchymal transition(EMT)is involved in both physiological and pathological processes.EMT plays an essential role in the invasion,migration and metastasis of tumours.Autophagy has been shown to regulate EMT in a variety of cancers but not in head and neck squamous cell carcinoma(HNSCC).Herein,we investigated whether autophagy also regulates EMT in HNSCC.Analyses of clinical data from three public databases revealed that higher expression of fibronectin-1(FN1)correlated with poorer prognosis and higher tumour pathological grade in HNSCC.Data from SCC-25 cells demonstrated that rapamycin and Earle’s balanced salt solution(EBSS)promoted autophagy,leading to increased FN1 degradation,while 3-methyladenine(3-MA),bafilomycin A1(Baf A1)and chloroquine(CQ)inhibited autophagy,leading to decreased FN1 degradation.On the other hand,autophagic flux was blocked in BECN1 mutant HNSCC Cal-27 cells,and rapamycin did not promote autophagy in Cal-27 cells;also in addition,FN1 degradation was inhibited.Further,we identified FN1 degradation through the lysosome-dependent degradation pathway using the proteasome inhibitor MG132.Data from immunoprecipitation assays also showed that p62/SQSTM1 participated as an autophagy adapter in the autophagy–lysosome pathway of FN1 degradation.Finally,data from immunoprecipitation assays demonstrated that the interaction between p62 and FN1 was abolished in p62 mutant MCF-7 and A2780 cell lines.These results indicate that autophagy significantly promotes the degradation of FN1.Collectively,our findings clearly suggest that FN1,as a marker of EMT,has adverse effects on HNSCC and elucidate the autophagy–lysosome degradation mechanism of FN1.展开更多
[目的]探究纤维连接蛋白1(Fibronectin 1,FN1)在多形性胶质母细胞瘤(GBM)中的表达情况及对患者预后的影响,为GBM的早期诊断和治疗提供生物标志物。[方法]CCLE数据库分析FN1在不同肿瘤细胞系中的表达;UALCAN和GEPIA2数据库分析FN1在GBM...[目的]探究纤维连接蛋白1(Fibronectin 1,FN1)在多形性胶质母细胞瘤(GBM)中的表达情况及对患者预后的影响,为GBM的早期诊断和治疗提供生物标志物。[方法]CCLE数据库分析FN1在不同肿瘤细胞系中的表达;UALCAN和GEPIA2数据库分析FN1在GBM肿瘤组织和正常组织中的表达差异;The Human Protein Atlas数据库分析FN1蛋白在GBM肿瘤组织和正常组织中的表达;GEPIA2数据库分析FN1在肿瘤组织中的异常表达对GBM患者总体生存率和无病生存率的影响;DAVID 6.8在线软件对FN1相关基因进行KEGG通路富集。[结果]在所有类型肿瘤细胞系中,GBM肿瘤细胞系中FN1 mRNA表达水平中排第八;FN1在GBM肿瘤组织中的表达高于正常组织(***P<0.001和*P<0.05),并且FN1高表达后GBM患者的总体生存率和无病生存率均降低(P=0.028和P=0.0056);KEGG分析结果表明与FN1正相关的基因富集通路有57个,癌症通路位于第三位。[结论]FN1在GBM中明显上调,是GBM诊断和预后的有效生物标志物。展开更多
基金This work was supported by grants from the National Natural Science Foundation of China(881320108011,81600823,81920108012,81870741)China Postdoctoral Science Foundation(2017M611332,2019M661177)+2 种基金Provincial Science Foundation of Jilin Provincial Department of Finance(JLS22019378-28)Bethune Project of Jilin University(2018A06,2015340)Jilin Scientific and Technological Development Programme(20170101093JC).
文摘Epithelial–mesenchymal transition(EMT)is involved in both physiological and pathological processes.EMT plays an essential role in the invasion,migration and metastasis of tumours.Autophagy has been shown to regulate EMT in a variety of cancers but not in head and neck squamous cell carcinoma(HNSCC).Herein,we investigated whether autophagy also regulates EMT in HNSCC.Analyses of clinical data from three public databases revealed that higher expression of fibronectin-1(FN1)correlated with poorer prognosis and higher tumour pathological grade in HNSCC.Data from SCC-25 cells demonstrated that rapamycin and Earle’s balanced salt solution(EBSS)promoted autophagy,leading to increased FN1 degradation,while 3-methyladenine(3-MA),bafilomycin A1(Baf A1)and chloroquine(CQ)inhibited autophagy,leading to decreased FN1 degradation.On the other hand,autophagic flux was blocked in BECN1 mutant HNSCC Cal-27 cells,and rapamycin did not promote autophagy in Cal-27 cells;also in addition,FN1 degradation was inhibited.Further,we identified FN1 degradation through the lysosome-dependent degradation pathway using the proteasome inhibitor MG132.Data from immunoprecipitation assays also showed that p62/SQSTM1 participated as an autophagy adapter in the autophagy–lysosome pathway of FN1 degradation.Finally,data from immunoprecipitation assays demonstrated that the interaction between p62 and FN1 was abolished in p62 mutant MCF-7 and A2780 cell lines.These results indicate that autophagy significantly promotes the degradation of FN1.Collectively,our findings clearly suggest that FN1,as a marker of EMT,has adverse effects on HNSCC and elucidate the autophagy–lysosome degradation mechanism of FN1.
文摘[目的]探究纤维连接蛋白1(Fibronectin 1,FN1)在多形性胶质母细胞瘤(GBM)中的表达情况及对患者预后的影响,为GBM的早期诊断和治疗提供生物标志物。[方法]CCLE数据库分析FN1在不同肿瘤细胞系中的表达;UALCAN和GEPIA2数据库分析FN1在GBM肿瘤组织和正常组织中的表达差异;The Human Protein Atlas数据库分析FN1蛋白在GBM肿瘤组织和正常组织中的表达;GEPIA2数据库分析FN1在肿瘤组织中的异常表达对GBM患者总体生存率和无病生存率的影响;DAVID 6.8在线软件对FN1相关基因进行KEGG通路富集。[结果]在所有类型肿瘤细胞系中,GBM肿瘤细胞系中FN1 mRNA表达水平中排第八;FN1在GBM肿瘤组织中的表达高于正常组织(***P<0.001和*P<0.05),并且FN1高表达后GBM患者的总体生存率和无病生存率均降低(P=0.028和P=0.0056);KEGG分析结果表明与FN1正相关的基因富集通路有57个,癌症通路位于第三位。[结论]FN1在GBM中明显上调,是GBM诊断和预后的有效生物标志物。
