背景与目的已有研究发现转移相关蛋白2(metastasis-associated protein 2,MTA2)在多种肿瘤细胞系中表达且与肿瘤侵袭转移密切相关。本研究旨在研究MTA2在非小细胞肺癌(non-smallcel llungcancer,NSCLC)中的表达,并探讨MTA2表达与临床病...背景与目的已有研究发现转移相关蛋白2(metastasis-associated protein 2,MTA2)在多种肿瘤细胞系中表达且与肿瘤侵袭转移密切相关。本研究旨在研究MTA2在非小细胞肺癌(non-smallcel llungcancer,NSCLC)中的表达,并探讨MTA2表达与临床病理特征的关系。方法采用免疫组织化学(SP)方法检测110例非小细胞肺癌标本及34例癌旁肺组织中MTA2蛋白表达,并统计分析其表达与NSCLC临床病理特征关系。结果 MTA2在癌旁肺支气管上皮和肺泡上皮中无表达,在部分NSCLC中呈阳性表达。110例NSCLC标本中MTA2阳性表达率为58.18%(64/110),MTA2阳性表达与NSCLC的分化程度呈负相关,与临床分期、淋巴结转移呈正相关(P<0.05),与年龄、性别、NSCLC的病理分型无明显相关性(P>0.05)。结论 MTA2蛋白在部分NSCLC中呈阳性表达且与其分化程度、临床分期、淋巴结转移密切相关,提示肺癌的发生发展可能与MTA2有关,MTA2可能是肺癌新的标志物及治疗靶点。展开更多
目的探讨转移相关蛋白2(metastasis-associated protein 2,MTA2)在喉鳞状细胞癌组织中的表达,分析其与临床病理特征和患者预后的关系。方法采用免疫组化SP法检测120例喉石蜡包埋组织中MTA2蛋白的表达,采用Western blot法检测喉新鲜组织...目的探讨转移相关蛋白2(metastasis-associated protein 2,MTA2)在喉鳞状细胞癌组织中的表达,分析其与临床病理特征和患者预后的关系。方法采用免疫组化SP法检测120例喉石蜡包埋组织中MTA2蛋白的表达,采用Western blot法检测喉新鲜组织中MTA2蛋白的表达量,利用Kaplan-Meier法绘制总生存期曲线,Log-rank方法分析两组生存曲线差异,Cox比例风险回归模型筛选喉鳞状细胞癌患者的预后影响因素。结果MTA2在正常喉组织、高级别鳞状上皮内病变和喉鳞状细胞癌组织中的阳性率分别为6.67%、43.33%和73.33%,差异有统计学意义(χ^2=36.11,P<0.001),MTA2表达与喉鳞状细胞癌组织学分级、临床分期及淋巴结转移显著相关(P均<0.05);在正常喉组织、高级别鳞状上皮内病变及喉鳞状细胞癌组织中MTA2的相对表达量分别是0.98±0.07、1.30±0.07和1.46±0.11,差异有统计学意义(F=121.194,P<0.001);Kaplan-Meier生存分析提示MTA2表达与喉鳞状细胞癌患者的生存期显著相关(P<0.05);多因素回归分析表明MTA2蛋白表达、临床分期及淋巴结转移是喉鳞状细胞癌患者有效的独立预后指标(P均<0.05)。结论MTA2过表达在喉鳞状细胞癌发生、进展过程中发挥重要作用,可作为喉鳞状细胞癌独立的预后因素,MTA2有望成为指导喉鳞状细胞癌治疗和判断患者预后的新分子学标志物。展开更多
In order to investigate the roles of MTA2 in the pathogenesis of ovarian epithelial cancer, the expression of MTA2 in 4 ovarian cell lines were detected by semi-quantitative RT-PCR and Western-blot assays. MTA2 expres...In order to investigate the roles of MTA2 in the pathogenesis of ovarian epithelial cancer, the expression of MTA2 in 4 ovarian cell lines were detected by semi-quantitative RT-PCR and Western-blot assays. MTA2 expression in normal, borderline, benign and malignant epithelial ovarian tissues was immunohistochemically examined. The expression of MTA2 mRNA and protein was detected in all of 4 cell lines of ovarian epithelial cancer. The expression of MTA2 mRNA and protein was higher in strong migration cell lines than in weak migration ones. In borderline and ma lignant ovarian tissues tested, MTA2 staining was dramatically stronger than in normal and benign tissues （P〈0. 01）. The expression levels in malignant ovarian tissues were significantly higher than that in borderline epithelial ovarian tissues （P〈0.01）. The expression of MTA2 was correlated with clinical stage, histopathological grade and lymph node metastasis. It was concluded that the high expression of MTA2 was associated with more aggressive behaviors of epithelial ovarian cancer. MTA2 provides a novel indicator of ovarian cancer.展开更多
Objective:Angiogenesis plays a vital role in tumor growth and metastasis.Here,we aimed to find novel efficient antiangiogenic molecules targeting vascular endothelial growth factor A(VEGFA)at the transcriptional level...Objective:Angiogenesis plays a vital role in tumor growth and metastasis.Here,we aimed to find novel efficient antiangiogenic molecules targeting vascular endothelial growth factor A(VEGFA)at the transcriptional level to treat triple-negative breast cancer(TNBC).Methods:We used a cell-based seryl tRNA synthetase(SerRS)promoter-driven dual-luciferase reporter system to screen an in-house library of 384 naturally occurring small molecules and their derivatives to find candidate molecules that could upregulate the expression of SerRS,a potent transcriptional repressor of VEGFA.The levels of SerRS and VEGFA were examined by quantitative RT-PCR(qRT-PCR),western blotting,and/or ELISAs in TNBC cells after candidate molecule administration.Zebrafish,the Matrigel plug angiogenesis assay in mice,the TNBC allograft,and xenograft mouse models were used to evaluate thein vivoanti-angiogenic and anti-cancer activities.Furthermore,the potential direct targets of the candidates were identified by proteomics and biochemical studies.Results:We found the most active compound was 3-(4-methoxyphenyl)quinolin-4(1H)-one(MEQ),an isoflavone derivative.In TNBC cells,MEQ treatment resulted in increased SerRS mRNA(P<0.001)and protein levels and downregulated VEGFA production.Both the vascular development of zebrafish and Matrigel plug angiogenesis in mice were inhibited by MEQ.MEQ also suppressed the angiogenesis in TNBC allografts and xenografts in mice,resulting in inhibited tumor growth and prolonged overall survival(P<0.05).Finally,we found that MEQ regulated SerRS transcription by interacting with MTA2(Metastasis Associated 1 Family Member 2).Conclusions:Our findings suggested that the MTA2/SerRS/VEGFA axis is a drug-treatable anti-angiogenic target,and MEQ is a promising anti-tumor molecule that merits further investigation for clinical applications.展开更多
Dear editor,MTA2 is associated with invasively malignant phenotypes in many types of cancers,1 but the molecular mechanism remains unclear.Studies on the role of MTA2 mostly concentrated on it as a component of the Nu...Dear editor,MTA2 is associated with invasively malignant phenotypes in many types of cancers,1 but the molecular mechanism remains unclear.Studies on the role of MTA2 mostly concentrated on it as a component of the NuRD complex,which functions via the NuRD complex to inhibit the transcription of downstream target genes.2 Whether MTA2 could directly exert transcriptional regulation independent of the transcription factor remains unclear and is the focus of the present study.展开更多
文摘目的探讨转移相关蛋白2(metastasis-associated protein 2,MTA2)在喉鳞状细胞癌组织中的表达,分析其与临床病理特征和患者预后的关系。方法采用免疫组化SP法检测120例喉石蜡包埋组织中MTA2蛋白的表达,采用Western blot法检测喉新鲜组织中MTA2蛋白的表达量,利用Kaplan-Meier法绘制总生存期曲线,Log-rank方法分析两组生存曲线差异,Cox比例风险回归模型筛选喉鳞状细胞癌患者的预后影响因素。结果MTA2在正常喉组织、高级别鳞状上皮内病变和喉鳞状细胞癌组织中的阳性率分别为6.67%、43.33%和73.33%,差异有统计学意义(χ^2=36.11,P<0.001),MTA2表达与喉鳞状细胞癌组织学分级、临床分期及淋巴结转移显著相关(P均<0.05);在正常喉组织、高级别鳞状上皮内病变及喉鳞状细胞癌组织中MTA2的相对表达量分别是0.98±0.07、1.30±0.07和1.46±0.11,差异有统计学意义(F=121.194,P<0.001);Kaplan-Meier生存分析提示MTA2表达与喉鳞状细胞癌患者的生存期显著相关(P<0.05);多因素回归分析表明MTA2蛋白表达、临床分期及淋巴结转移是喉鳞状细胞癌患者有效的独立预后指标(P均<0.05)。结论MTA2过表达在喉鳞状细胞癌发生、进展过程中发挥重要作用,可作为喉鳞状细胞癌独立的预后因素,MTA2有望成为指导喉鳞状细胞癌治疗和判断患者预后的新分子学标志物。
文摘In order to investigate the roles of MTA2 in the pathogenesis of ovarian epithelial cancer, the expression of MTA2 in 4 ovarian cell lines were detected by semi-quantitative RT-PCR and Western-blot assays. MTA2 expression in normal, borderline, benign and malignant epithelial ovarian tissues was immunohistochemically examined. The expression of MTA2 mRNA and protein was detected in all of 4 cell lines of ovarian epithelial cancer. The expression of MTA2 mRNA and protein was higher in strong migration cell lines than in weak migration ones. In borderline and ma lignant ovarian tissues tested, MTA2 staining was dramatically stronger than in normal and benign tissues （P〈0. 01）. The expression levels in malignant ovarian tissues were significantly higher than that in borderline epithelial ovarian tissues （P〈0.01）. The expression of MTA2 was correlated with clinical stage, histopathological grade and lymph node metastasis. It was concluded that the high expression of MTA2 was associated with more aggressive behaviors of epithelial ovarian cancer. MTA2 provides a novel indicator of ovarian cancer.
基金This work was supported by grants from the National Natural Science Foundation of China(Grant Nos.81772974,81972882,and 81874297)the Bilateral Inter-Governmental S&T Cooperation Project from Ministry of Science and Technology of China(Grant No.2018YFE0114300)+2 种基金the 1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University.We thank Dr.Scott McKercher(The Scripps Research Institute,La Jolla,CA,USA)Dr.Phillip Bryant(Childrens Hospital of Philadelphia,PA,USA)Dr.Cameron R.McKay(Nankai University School of Medicine,Tianjin,China)for revising the manuscript.
文摘Objective:Angiogenesis plays a vital role in tumor growth and metastasis.Here,we aimed to find novel efficient antiangiogenic molecules targeting vascular endothelial growth factor A(VEGFA)at the transcriptional level to treat triple-negative breast cancer(TNBC).Methods:We used a cell-based seryl tRNA synthetase(SerRS)promoter-driven dual-luciferase reporter system to screen an in-house library of 384 naturally occurring small molecules and their derivatives to find candidate molecules that could upregulate the expression of SerRS,a potent transcriptional repressor of VEGFA.The levels of SerRS and VEGFA were examined by quantitative RT-PCR(qRT-PCR),western blotting,and/or ELISAs in TNBC cells after candidate molecule administration.Zebrafish,the Matrigel plug angiogenesis assay in mice,the TNBC allograft,and xenograft mouse models were used to evaluate thein vivoanti-angiogenic and anti-cancer activities.Furthermore,the potential direct targets of the candidates were identified by proteomics and biochemical studies.Results:We found the most active compound was 3-(4-methoxyphenyl)quinolin-4(1H)-one(MEQ),an isoflavone derivative.In TNBC cells,MEQ treatment resulted in increased SerRS mRNA(P<0.001)and protein levels and downregulated VEGFA production.Both the vascular development of zebrafish and Matrigel plug angiogenesis in mice were inhibited by MEQ.MEQ also suppressed the angiogenesis in TNBC allografts and xenografts in mice,resulting in inhibited tumor growth and prolonged overall survival(P<0.05).Finally,we found that MEQ regulated SerRS transcription by interacting with MTA2(Metastasis Associated 1 Family Member 2).Conclusions:Our findings suggested that the MTA2/SerRS/VEGFA axis is a drug-treatable anti-angiogenic target,and MEQ is a promising anti-tumor molecule that merits further investigation for clinical applications.
基金This study was supported by the National Science and Technology Major Project(Grant No.2018ZX09736005)National Natural Science Foundation of China(grant no.81872374,81972629,81972746,82073205,82072709,81902441)+1 种基金Tianjin Science and Technology Project(Grant No.19JCJQJC63200)the Taishan Scholars Program of Shandong Province(Grant No.tsqn201909193).
文摘Dear editor,MTA2 is associated with invasively malignant phenotypes in many types of cancers,1 but the molecular mechanism remains unclear.Studies on the role of MTA2 mostly concentrated on it as a component of the NuRD complex,which functions via the NuRD complex to inhibit the transcription of downstream target genes.2 Whether MTA2 could directly exert transcriptional regulation independent of the transcription factor remains unclear and is the focus of the present study.
