共查询到20条相似文献,搜索用时 15 毫秒
1.
MicroRNA-10b and breast cancer metastasis 总被引:1,自引:0,他引:1
Gee HE Camps C Buffa FM Colella S Sheldon H Gleadle JM Ragoussis J Harris AL 《Nature》2008,455(7216):E8-9; author reply E9
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Involvement of chemokine receptors in breast cancer metastasis 总被引:344,自引:0,他引:344
Müller A Homey B Soto H Ge N Catron D Buchanan ME McClanahan T Murphy E Yuan W Wagner SN Barrera JL Mohar A Verástegui E Zlotnik A 《Nature》2001,410(6824):50-56
Breast cancer is characterized by a distinct metastatic pattern involving the regional lymph nodes, bone marrow, lung and liver. Tumour cell migration and metastasis share many similarities with leukocyte trafficking, which is critically regulated by chemokines and their receptors. Here we report that the chemokine receptors CXCR4 and CCR7 are highly expressed in human breast cancer cells, malignant breast tumours and metastases. Their respective ligands CXCL12/SDF-1alpha and CCL21/6Ckine exhibit peak levels of expression in organs representing the first destinations of breast cancer metastasis. In breast cancer cells, signalling through CXCR4 or CCR7 mediates actin polymerization and pseudopodia formation, and subsequently induces chemotactic and invasive responses. In vivo, neutralizing the interactions of CXCL12/CXCR4 significantly impairs metastasis of breast cancer cells to regional lymph nodes and lung. Malignant melanoma, which has a similar metastatic pattern as breast cancer but also a high incidence of skin metastases, shows high expression levels of CCR10 in addition to CXCR4 and CCR7. Our findings indicate that chemokines and their receptors have a critical role in determining the metastatic destination of tumour cells. 相似文献
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MicroRNAs(miRs) have been shown to be differentially expressed in the serum of cancer patients and controls,and can thus be used as biomarkers for cancer screening.We detected the expression level of miR-155 in the serum of female breast cancer patients and healthy controls to investigate whether serum miR-155 could discriminate patients with early-stage breast cancer.Serum samples were collected from 20 female patients with newly diagnosed breast cancer and 10 healthy controls.Real-time quantitative PCR was used to detect the expression level of miR-155.The expression level of miR-155 was significantly increased in the serum of breast cancer patients compared with in the serum of normal controls.MiR-155 may be useful as a blood-based biomarker for breast cancer screening. 相似文献
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M Montagner E Enzo M Forcato F Zanconato A Parenti E Rampazzo G Basso G Leo A Rosato S Bicciato M Cordenonsi S Piccolo 《Nature》2012,487(7407):380-384
The molecular determinants of malignant cell behaviours in breast cancer remain only partially understood. Here we show that SHARP1 (also known as BHLHE41 or DEC2) is a crucial regulator of the invasive and metastatic phenotype in triple-negative breast cancer (TNBC), one of the most aggressive types of breast cancer. SHARP1 is regulated by the p63 metastasis suppressor and inhibits TNBC aggressiveness through inhibition of hypoxia-inducible factor 1α (HIF-1α) and HIF-2α (HIFs). SHARP1 opposes HIF-dependent TNBC cell migration in vitro, and invasive or metastatic behaviours in vivo. SHARP1 is required, and sufficient, to limit expression of HIF-target genes. In primary TNBC, endogenous SHARP1 levels are inversely correlated with those of HIF targets. Mechanistically, SHARP1 binds to HIFs and promotes HIF proteasomal degradation by serving as the HIF-presenting factor to the proteasome. This process is independent of pVHL (von Hippel-Lindau tumour suppressor), hypoxia and the ubiquitination machinery. SHARP1 therefore determines the intrinsic instability of HIF proteins to act in parallel to, and cooperate with, oxygen levels. This work sheds light on the mechanisms and pathways by which TNBC acquires invasiveness and metastatic propensity. 相似文献
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Tavazoie SF Alarcón C Oskarsson T Padua D Wang Q Bos PD Gerald WL Massagué J 《Nature》2008,451(7175):147-152
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口腔癌转移是威胁全世界生命健康的问题,有效的靶向治疗对口腔癌患者尤为重要.近年来,microRNA(miRNA)作为一种微小的非编码RNA在肿瘤转移中发挥着重要的作用,因此,开展了体外探究miR-23b在口腔癌转移中的作用.利用实时荧光定量核酸扩增检测系统(qRT-PCR)检测了miR-23b在口腔正常细胞和口腔癌细胞中的表达差异,结果显示miR-23b在口腔癌细胞中的表达明显高于口腔正常细胞中的表达,且随着口腔癌转移程度的增加而增高(P<0.05).在此基础上,通过给细胞转染miR-23b mimics的方法过表达miR-23b,以探究该miRNA对口腔癌转移的作用.实验结果发现,增加口腔原位癌细胞Um-2中miR-23b的表达后,该细胞的转移能力显著增强,表明miR-23b在口腔癌转移中发挥着重要作用,可能成为临床口腔癌的治疗靶点和口腔癌检测标志物. 相似文献
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Karnoub AE Dash AB Vo AP Sullivan A Brooks MW Bell GW Richardson AL Polyak K Tubo R Weinberg RA 《Nature》2007,449(7162):557-563
Mesenchymal stem cells have been recently described to localize to breast carcinomas, where they integrate into the tumour-associated stroma. However, the involvement of mesenchymal stem cells (or their derivatives) in tumour pathophysiology has not been addressed. Here, we demonstrate that bone-marrow-derived human mesenchymal stem cells, when mixed with otherwise weakly metastatic human breast carcinoma cells, cause the cancer cells to increase their metastatic potency greatly when this cell mixture is introduced into a subcutaneous site and allowed to form a tumour xenograft. The breast cancer cells stimulate de novo secretion of the chemokine CCL5 (also called RANTES) from mesenchymal stem cells, which then acts in a paracrine fashion on the cancer cells to enhance their motility, invasion and metastasis. This enhanced metastatic ability is reversible and is dependent on CCL5 signalling through the chemokine receptor CCR5. Collectively, these data demonstrate that the tumour microenvironment facilitates metastatic spread by eliciting reversible changes in the phenotype of cancer cells. 相似文献
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乳腺癌脑转移(breast cancer brain metastasis,BCBM)的发病机制尚未明确。为了探究BCBM的发病机制,对BCBM差异表达基因的生物学功能进行研究并筛选关键调控基因。从基因表达综合数据库(gene expression omnibus,GEO)下载4个BCBM基因表达谱数据(GSE12237、GSE100534、GSE125989以及GSE43837),采用R语言筛选差异表达基因,采用富集分析包括基因本体分析(gene ontology,GO)和京都基因与基因组百科全书分析(Kyoto encyclopedia of genes and genomes,KEGG)进行生物学功能分析,采用STRING和Cytoscape分析蛋白质相互作用网络,采用Kaplan-Meier进行生存分析。结果表明,同时存在于2个及以上基因表达谱数据中的差异表达基因261个,GO分析主要涉及细胞外基质组织、细胞外结构组织等生物过程,细胞外基质结构组成、胶原结合等分子功能,含有胶原的细胞外基质、胶原蛋白三聚物等细胞组分;KEGG分析主要涉及蛋白质消化和吸收、局部黏附等通路。蛋白质相互作用网络分析得到9个关键调控基因,其中,DCN、COL6A1与BCBM的生存率显著相关,可作为潜在的BCBM关键调控基因,并为BCBM分子机制的研究提供思路。 相似文献
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基质金属蛋白酶是一类锌离子依赖的、能够降解细胞外基质的内肽酶,它通过降解细胞外基质促进肿瘤细胞的侵袭和转移;现就基质金属蛋白酶在肿瘤细胞侵袭和转移过程中的作用以及基质金属蛋白酶与临床恶性肿瘤的相关性进行简单综述。 相似文献
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基质金属蛋白酶与肿瘤的侵袭和转移 总被引:2,自引:0,他引:2
肿瘤侵袭和转移是一个相当复杂的过程,现在的观点认为基质金属蛋白酶(matrix metallo proteinases,MMP)在此过程中起重要作用,就近年来的有关文献,对MMP与肿瘤侵袭和转移的关系以及相关药物最新进展进行综述。 相似文献
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Jones DH Nakashima T Sanchez OH Kozieradzki I Komarova SV Sarosi I Morony S Rubin E Sarao R Hojilla CV Komnenovic V Kong YY Schreiber M Dixon SJ Sims SM Khokha R Wada T Penninger JM 《Nature》2006,440(7084):692-696
Bone metastases are a frequent complication of many cancers that result in severe disease burden and pain. Since the late nineteenth century, it has been thought that the microenvironment of the local host tissue actively participates in the propensity of certain cancers to metastasize to specific organs, and that bone provides an especially fertile 'soil'. In the case of breast cancers, the local chemokine milieu is now emerging as an explanation for why these tumours preferentially metastasize to certain organs. However, as the inhibition of chemokine receptors in vivo only partially blocks metastatic behaviour, other factors must exist that regulate the preferential metastasis of breast cancer cells. Here we show that the cytokine RANKL (receptor activator of NF-kappaB ligand) triggers migration of human epithelial cancer cells and melanoma cells that express the receptor RANK. RANK is expressed on cancer cell lines and breast cancer cells in patients. In a mouse model of melanoma metastasis, in vivo neutralization of RANKL by osteoprotegerin results in complete protection from paralysis and a marked reduction in tumour burden in bones but not in other organs. Our data show that local differentiation factors such as RANKL have an important role in cell migration and the tissue-specific metastatic behaviour of cancer cells. 相似文献
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QingLing Yang YongXing Ding ChangJie Chen Jie Tang Ju Zhang ZhiFeng Yang 《科学通报(英文版)》2010,55(20):2152-2159
Stromal cell-derived factor-1 and its receptor CXC chemokine receptor-4 (CXCR4) have been implicated in breast cancer metastasis. A significant association between HER2 and CXCR4 expression has been observed in human breast tumor tissues, and overexpression of CXCR4 is essential for HER2-mediated tumor metastasis. Moreover, CXCR4 expression is low in normal breast tissues and high in malignant tumors, suggesting that a blockade of CXCR4 may limit tumor metastasis. The present study investigated the action of a synthetic antagonist 21-mer peptide derived from viral macrophage inflammatory protein II against CXCR4 (NT21MP) in inhibiting metastasis in vitro and in vivo. The results showed that chemotaxis of SKBR3 cells toward SDF-1α was reduced by NT21MP in a dose-dependent manner (P < 0.05). NT21MP inhibited tumor growth at 500 μg/kg and in combination with Herceptin, the anti-HER2 antibody. The in vivo metastatic assay showed that NT21MP significantly inhibited pulmonary metastasis, and the number of metastatic tumor nodes on the surface of the lung was greatly decreased. Compared with the saline-treated control group, PCNA expression was dose-dependently decreased by NT21MP, the percentage of apoptotic cells was increased, and CXCR4 mRNA and protein expression were downregulated. In conclusion, NT21MP inhibits cellular prolifer-ation, promotes apoptosis by downregulating CXCR4 expression, and suppresses the progression of primary and metastatic tumors. CXCR4 may be a useful therapeutic target for breast cancer, and NT21MP may serve as a potential target drug for the treatment of breast cancer metastasis. 相似文献
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A microRNA regulon that mediates endothelial recruitment and metastasis by cancer cells 总被引:1,自引:0,他引:1
Metastatic progression of cancer is a complex and clinically daunting process. We previously identified a set of human microRNAs (miRNAs) that robustly suppress breast cancer metastasis to lung and bone and which display expression levels that predict human metastasis. Although these findings revealed miRNAs as suppressors of cell-autonomous metastatic phenotypes, the roles of non-coding RNAs in non-cell-autonomous cancer progression processes remain unknown. Here we reveal that endogenous miR-126, an miRNA silenced in a variety of common human cancers, non-cell-autonomously regulates endothelial cell recruitment to metastatic breast cancer cells, in vitro and in vivo. It suppresses metastatic endothelial recruitment, metastatic angiogenesis and metastatic colonization through coordinate targeting of IGFBP2, PITPNC1 and MERTK--novel pro-angiogenic genes and biomarkers of human metastasis. Insulin-like growth factor binding protein 2 (IGFBP2) secreted by metastatic cells recruits endothelia by modulating IGF1-mediated activation of the IGF type-I receptor on endothelial cells; whereas c-Mer tyrosine kinase (MERTK) receptor cleaved from metastatic cells promotes endothelial recruitment by competitively antagonizing the binding of its ligand GAS6 to endothelial MERTK receptors. Co-injection of endothelial cells with breast cancer cells non-cell-autonomously rescues their miR-126-induced metastatic defect, revealing a novel and important role for endothelial interactions in metastatic initiation. Through loss-of-function and epistasis experiments, we delineate an miRNA regulatory network's individual components as novel and cell-extrinsic regulators of endothelial recruitment, angiogenesis and metastatic colonization. We also identify the IGFBP2/IGF1/IGF1R and GAS6/MERTK signalling pathways as regulators of cancer-mediated endothelial recruitment. Our work further reveals endothelial recruitment and endothelial interactions in the tumour microenvironment to be critical features of metastatic breast cancer. 相似文献
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LKB1 modulates lung cancer differentiation and metastasis 总被引:1,自引:0,他引:1
Ji H Ramsey MR Hayes DN Fan C McNamara K Kozlowski P Torrice C Wu MC Shimamura T Perera SA Liang MC Cai D Naumov GN Bao L Contreras CM Li D Chen L Krishnamurthy J Koivunen J Chirieac LR Padera RF Bronson RT Lindeman NI Christiani DC Lin X Shapiro GI Jänne PA Johnson BE Meyerson M Kwiatkowski DJ Castrillon DH Bardeesy N Sharpless NE Wong KK 《Nature》2007,448(7155):807-810
Germline mutation in serine/threonine kinase 11 (STK11, also called LKB1) results in Peutz-Jeghers syndrome, characterized by intestinal hamartomas and increased incidence of epithelial cancers. Although uncommon in most sporadic cancers, inactivating somatic mutations of LKB1 have been reported in primary human lung adenocarcinomas and derivative cell lines. Here we used a somatically activatable mutant Kras-driven model of mouse lung cancer to compare the role of Lkb1 to other tumour suppressors in lung cancer. Although Kras mutation cooperated with loss of p53 or Ink4a/Arf (also known as Cdkn2a) in this system, the strongest cooperation was seen with homozygous inactivation of Lkb1. Lkb1-deficient tumours demonstrated shorter latency, an expanded histological spectrum (adeno-, squamous and large-cell carcinoma) and more frequent metastasis compared to tumours lacking p53 or Ink4a/Arf. Pulmonary tumorigenesis was also accelerated by hemizygous inactivation of Lkb1. Consistent with these findings, inactivation of LKB1 was found in 34% and 19% of 144 analysed human lung adenocarcinomas and squamous cell carcinomas, respectively. Expression profiling in human lung cancer cell lines and mouse lung tumours identified a variety of metastasis-promoting genes, such as NEDD9, VEGFC and CD24, as targets of LKB1 repression in lung cancer. These studies establish LKB1 as a critical barrier to pulmonary tumorigenesis, controlling initiation, differentiation and metastasis. 相似文献
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LVDS在高速数据传输中得到了广泛应用,但在传输过程中存在交流耦合,使得连续出现的0或1信号传输会出现丢数、误码等问题。通过介绍直流平衡在交流耦合中的作用,采用8b/10b编码的方法,实现了直流平衡。同时说明了8b/10b编码的具体实现过程中的重点和细节。通过仿真和实际数据收发,证实了该方案的可行性、准确性,提高了LVDS数据传输能力。 相似文献
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基于电阻抗扫描成像的乳腺癌检测方法 总被引:1,自引:1,他引:0
为了提高电阻抗成像在乳腺癌检测方面的性能,降低其假阳性率,提出了一种新的乳腺癌检测算子———异常能量指标(AEI)检测乳腺癌.通过对乳腺电阻抗成像进行建模并结合优化问题求解,提取乳腺癌病灶参数并进而构造AEI指标.与传统的基于临床医师视觉解释的图像检测方法相比,新方法可以获得更高的灵敏度、特异度和准确度.与基于参数的乳腺癌检测算法(HEDA算法和P算法)相比,AEI指标用于乳腺癌检测具有较高的灵敏度及特异度.临床数据实验表明,新方法可以有效地用于乳腺癌检测,具有较好的检测性能(灵敏度88.5%、特异度89.1%以及准确度88.9%). 相似文献
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Stephens PJ Tarpey PS Davies H Van Loo P Greenman C Wedge DC Nik-Zainal S Martin S Varela I Bignell GR Yates LR Papaemmanuil E Beare D Butler A Cheverton A Gamble J Hinton J Jia M Jayakumar A Jones D Latimer C Lau KW McLaren S McBride DJ Menzies A Mudie L Raine K Rad R Chapman MS Teague J Easton D Langerød A;Oslo Breast Cancer Consortium 《Nature》2012,486(7403):400-404
All cancers carry somatic mutations in their genomes. A subset, known as driver mutations, confer clonal selective advantage on cancer cells and are causally implicated in oncogenesis, and the remainder are passenger mutations. The driver mutations and mutational processes operative in breast cancer have not yet been comprehensively explored. Here we examine the genomes of 100 tumours for somatic copy number changes and mutations in the coding exons of protein-coding genes. The number of somatic mutations varied markedly between individual tumours. We found strong correlations between mutation number, age at which cancer was diagnosed and cancer histological grade, and observed multiple mutational signatures, including one present in about ten per cent of tumours characterized by numerous mutations of cytosine at TpC dinucleotides. Driver mutations were identified in several new cancer genes including AKT2, ARID1B, CASP8, CDKN1B, MAP3K1, MAP3K13, NCOR1, SMARCD1 and TBX3. Among the 100 tumours, we found driver mutations in at least 40 cancer genes and 73 different combinations of mutated cancer genes. The results highlight the substantial genetic diversity underlying this common disease. 相似文献