Cancer cell & microenvironment最新文献_第9页

Sequential use of primary malignant circulating prostate cells to detect prostate cancer 顺序使用原发性恶性循环前列腺细胞检测前列腺癌

Cancer cell & microenvironment Pub Date : 2015-03-24 DOI: 10.14800/CCM.714

N. Murray, E. Reyes, C. Fuentealba, N. Orellana, O. Jacob

引用次数: 1

Suppressing the TF-fVII pathway at the gene expression level: A strategy to inhibit aberrant signaling cascades associated with cancer cells 在基因表达水平上抑制TF-fVII通路:一种抑制与癌细胞相关的异常信号级联的策略

Cancer cell & microenvironment Pub Date : 2015-03-24 DOI: 10.14800/CCM.734

S. Koizume, Y. Miyagi

{"title":"Suppressing the TF-fVII pathway at the gene expression level: A strategy to inhibit aberrant signaling cascades associated with cancer cells","authors":"S. Koizume, Y. Miyagi","doi":"10.14800/CCM.734","DOIUrl":"https://doi.org/10.14800/CCM.734","url":null,"abstract":"Normal human tissues widely synthesize tissue factor (TF), also known as coagulation factor III, on their surface. Coagulation factor VII (fVII) is a serine protease precursor, primarily produced by hepatocytes in the liver and secreted into the bloodstream. Upon injury, fVII in the blood can bind its cellular receptor, TF, converting to its active form, fVIIa. This TF-fVIIa complex initiates a downstream extrinsic coagulation cascade. Cancer cells are known to overexpress TF. Formation of a protein complex between cell surface TF and plasma fVII can trigger aberrant cellular signaling via multiple pathways, resulting in malignant phenotypes. In addition, the TF-fVIIa complex may underlie a common complication associated with particular cancer types, venous thromboembolism, suggesting that TF-fVIIa signaling may be an attractive therapeutic target. Basal transcription of TF ( F3 ) and fVII ( FVII ) genes in normal and cancer cells is regulated by the ubiquitous transcription factor, Sp1, and other tissue-specific transcription factors. Furthermore, the F3 gene may be activated in cancer cells in response to various stimuli associated with the tumor microenvironment. Intriguingly, FVII can be constitutively activated in non-hepatocytic cancer cells. Hypoxia, characteristic of the tumor microenvironment, can enhance expression of both F3 and FVII genes, but via distinct molecular mechanisms. In this short review, we will discuss strategies to suppress this aberrant transcription based on our current knowledge of the molecular mechanisms regulating gene expression. We will further discuss how these strategies are beneficial compared with those targeting the cell surface TF-fVIIa complex.","PeriodicalId":9576,"journal":{"name":"Cancer cell & microenvironment","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77219045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Helping the hypermutator: The Fhit-APOBEC connection 帮助超突变:Fhit-APOBEC连接

Cancer cell & microenvironment Pub Date : 2015-03-18 DOI: 10.14800/CCM.713

Catherine E. Waters, K. Huebner

{"title":"Helping the hypermutator: The Fhit-APOBEC connection","authors":"Catherine E. Waters, K. Huebner","doi":"10.14800/CCM.713","DOIUrl":"https://doi.org/10.14800/CCM.713","url":null,"abstract":"The APOBEC3B (A3B) somatic mutation signature (C>T point mutations at TC dinucleotides) is widespread in human cancers, but stratification of tumors based on A3B gene expression shows weak positive correlation with hypermutation. Further stratification with factors that increase the availability of ssDNA, the preferred substrate for A3B, will likely enhance this correlation and increase our understanding of the mechanisms behind this most pervasive mutational signature in human cancers. Alterations at the FHIT gene locus occur early in cancer initiation, leading to reduction or complete loss of Fhit protein expression in over 50% of cancers. Fhit loss causes replication stress and genome instability in cells without cell cycle arrest or apoptosis, allowing cells to accumulate DNA damage with each subsequent cell division. Thus, Fhit negative cells harbor increased availability of A3B target ssDNA, leading to our proposal that Fhit loss creates optimal A3B substrates that facilitate A3B-mediated mutagenesis. This research highlight summarizes our recent findings concerning the cooperation of Fhit loss-induced DNA damage and A3B overexpression. Briefly, DNA from FHIT deficient lung adenocarcinomas that also show high A3B expression exhibit the highest frequency of total mutations and A3B signature point mutations. In vitro , these mutations could be rescued by inhibiting the replication stress caused by Fhit loss. We also consider the role of Fhit loss itself in mutagenesis and what other enzymes may exploit Fhit loss-induced genome instability to increase mutagenesis. The recent advances in our understanding of A3B and Fhit loss-induced mutagenesis are applicable to the most common types of human cancers and involve events that occur at the very onset of cancer initiation.","PeriodicalId":9576,"journal":{"name":"Cancer cell & microenvironment","volume":"57 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74988462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A suppressor role for soluble endoglin in cancer 可溶性内啡肽在癌症中的抑制作用

Cancer cell & microenvironment Pub Date : 2015-03-16 DOI: 10.14800/CCM.706

M. Quintanilla, Gaelle del Castillo, E. Sánchez-Blanco, Ester Martín-Villar, A. C. Valbuena-Diez, C. Langa, E. Pérez-Gómez, J. Renart, C. Bernabéu

{"title":"A suppressor role for soluble endoglin in cancer","authors":"M. Quintanilla, Gaelle del Castillo, E. Sánchez-Blanco, Ester Martín-Villar, A. C. Valbuena-Diez, C. Langa, E. Pérez-Gómez, J. Renart, C. Bernabéu","doi":"10.14800/CCM.706","DOIUrl":"https://doi.org/10.14800/CCM.706","url":null,"abstract":"Elevated levels of a circulating form of the transforming growth factor-b (TGF-b) coreceptor endoglin correlate with poor clinical outcome in different types of cancer. Soluble endoglin (Sol-Eng) is primarily produced by cleavage of cell-surface endoglin by the transmembrane metalloprotease MMP14 that releases most of its extracellular domain. Sol-Eng has been found to contribute to different cardiovascular pathologies, including preeclampsia, a severe hypertensive syndrome of pregnancy. While the anti-angiogenic and pro-hypertensive functions of Sol-Eng appear well established, its role in cancer has not been fully investigated. Recently, we reported that Sol-Eng strongly inhibits signaling through the hepatocyte growth factor (HGF) tyrosine kinase receptor Met in mouse skin spindle carcinoma cells. Sol-Eng also blocked basal and HGF-mediated stimulation of carcinoma cell proliferation, migration and invasion. Taken together, the above results and the anti-angiogenic function exerted by Sol-Eng suggest a suppressor role for Sol-Eng in cancer. This conclusion is discussed in the paradoxical context of Sol-Eng as a marker of poor prognosis and as a potential contributor to the decreased risk of preeclamptic mothers to develop breast cancer later in life.","PeriodicalId":9576,"journal":{"name":"Cancer cell & microenvironment","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90455453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Novel markers of cancer stem cells in head and neck squamous cell carcinoma 头颈部鳞状细胞癌中肿瘤干细胞的新标志物

Cancer cell & microenvironment Pub Date : 2015-03-16 DOI: 10.14800/CCM.701

T. Fukusumi, H. Ishii, Jun Koseki, A. Hanamoto, S. Nakahara, Y. Yamamoto, H. Inohara

引用次数: 1

Linking the immunophilin FKBP5 to taxol resistance in ovarian cancer 亲免疫蛋白FKBP5与卵巢癌紫杉醇耐药的关系

Cancer cell & microenvironment Pub Date : 2015-03-16 DOI: 10.14800/CCM.692

Shang‐Lang Huang, C. Chao

{"title":"Linking the immunophilin FKBP5 to taxol resistance in ovarian cancer","authors":"Shang‐Lang Huang, C. Chao","doi":"10.14800/CCM.692","DOIUrl":"https://doi.org/10.14800/CCM.692","url":null,"abstract":"Taxol is a chemotherapeutic drug used to treat a number of cancers, including ovarian and breast cancers. However, taxol resistance limits treatment efficacy in cancer patients. To study the molecular mechanism of chemoresistance in ovarian cancer, we established taxol-resistant cells derived from the SKOV3 ovarian carcinoma cell lineage. Transcriptomic analysis identified 112 highly up-regulated genes in taxol-resistant cells. Among them, FK506-binding protein 5 (FKBP5) was transiently up-regulated 100 fold in taxol-resistant cells but showed reduced expression following prolonged culture. FKBP5 silencing sensitized taxol-resistant cells to taxol, while overexpression of FKBP5 increased resistance to the drug. We observed that several of the newly identified taxol resistance genes were trancriptionally regulated by FKBP5, and silencing of these genes sensitized cells to taxol. Our experiments also revealed that FKBP5 forms a protein complex with the androgen receptor (AR), and this complex regulates the transcriptional activity of both proteins. In addition, we observed that the Akt kinase pathway is regulated by FKBP5. These results indicate that the FKBP5/AR complex may affect cancer cell sensitivity to taxol by regulating expression of taxol resistance genes. Our results suggest that taxol should not be used against ovarian cancer when the Akt/FKBP5/AR axis is activated.","PeriodicalId":9576,"journal":{"name":"Cancer cell & microenvironment","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90186735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Developing docetaxel-loaded nanocapsules: A promising approach for cancer therapy 开发装载多西他赛的纳米胶囊:一种有前途的癌症治疗方法

Cancer cell & microenvironment Pub Date : 2015-03-06 DOI: 10.14800/CCM.689

I. Youm, V. Agrahari

{"title":"Developing docetaxel-loaded nanocapsules: A promising approach for cancer therapy","authors":"I. Youm, V. Agrahari","doi":"10.14800/CCM.689","DOIUrl":"https://doi.org/10.14800/CCM.689","url":null,"abstract":"This study has summarized the development of Docetaxel (DOC) loaded nanocapsules (NCs) intended for breast cancer (BC) therapy. These NCs are composed of a lipid core to encapsulate the hydrophobic DOC and a polymeric shell for surface functionalization. DOC was efficiently encapsulated within the oily core of NCs. The critical role of stabilizers on NCs stealthiness and anticancer drug efficacy was investigated. The potential impact of surface chemistry on the cytotoxicity and phagocytic clearance of NCs for a subsequent improvement of the efficacy of DOC in BC treatment was explored. The in vitro cell culture studies in cancer cell lines showed a significant enhancement of the cytotoxicity of DOC due to its high loading within the NCs. Interestingly, the NCs were stable during storage and could be efficiently transformed into powder form using freeze-drying method. It is also hypothesized that DOC-loaded hyaluronic acid (HA) grafted oily core NCs can enhance the drug cytotoxicity and uptake in CD44 expressing BC cells (MDA-MB 231). These novel nanostructures hold the promise to support the potential clinical application and cost-effectiveness of innovative nanotherapeutics in cancer therapy.","PeriodicalId":9576,"journal":{"name":"Cancer cell & microenvironment","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78815463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

How anti-angiogenic drugs are able to induce resistance to their own therapeutic effect in human metastatic renal carcinoma 在人类转移性肾癌中，抗血管生成药物如何能够诱导对其自身治疗效果的抵抗

Cancer cell & microenvironment Pub Date : 2015-03-03 DOI: 10.14800/CCM.669

G. Bousquet, A. Janin

引用次数: 0

Proton pump inhibitors as chemosensitizer: New indication for a well-known medication 质子泵抑制剂作为化学增敏剂:一种知名药物的新适应症

Cancer cell & microenvironment Pub Date : 2015-03-03 DOI: 10.14800/CCM.667

C. Matuszcak, K. Lindner, J. Haier, R. Hummel

引用次数: 6

Engagement, reception and breakup: Three steps of cell motility regulated by HPIP signaling 接合、接收和分离:HPIP信号调控的细胞运动的三个步骤

Cancer cell & microenvironment Pub Date : 2015-03-03 DOI: 10.14800/CCM.660

S. Bugide, B. Manavathi

{"title":"Engagement, reception and breakup: Three steps of cell motility regulated by HPIP signaling","authors":"S. Bugide, B. Manavathi","doi":"10.14800/CCM.660","DOIUrl":"https://doi.org/10.14800/CCM.660","url":null,"abstract":"Tumor metastasis is the prime cause for increased morbidity and mortality for majority of the cancers. Invasive or infiltrative ductal carcinoma (IDC) is the predominant form of breast cancer, accounting approximately 80% of all breast cancers. The molecular portraits and the mechanism by which they promote IDC remain largely unknown. Hematopoietic PBX interacting protein (HPIP/PBXIP1), a microtubule binding protein, regulates cancer cell migration and invasion. However, functional mechanism underlying HPIP-mediated cell migration in cancer remains uncertain. Here, we describe our recent studies in which we identified the new mechanisms by which HPIP regulates cell migration in breast cancer cells. Our recent studies confirmed that HPIP expression is elevated in breast infiltrative ductal carcinoma and positively correlated with poor patient survival. We reported that HPIP directly interacts and activates FAK to promote the cell migration. Mechanistic studies further revealed that HPIP induces focal adhesion disassembly by enhancing calpain2 activity through MAPK pathway that led to talin proteolysis, focal adhesion turnover and cell migration. Interestingly, the activated calpain2 in turn cleaves HPIP suggesting the tight regulation of HPIP-FAK-calpain2 signaling cascade during cell migration.","PeriodicalId":9576,"journal":{"name":"Cancer cell & microenvironment","volume":"55 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82758862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1