Journal of signal transduction最新文献_第7页

Involvement of Src in the Adaptation of Cancer Cells under Microenvironmental Stresses. Src参与癌细胞在微环境胁迫下的适应。

Journal of signal transduction Pub Date : 2012-01-01 Epub Date: 2012-09-03 DOI: 10.1155/2012/483796

A K M Mahbub Hasan, Takashi Ijiri, Ken-Ichi Sato

引用次数: 10

Nuclear transport: a switch for the oxidative stress-signaling circuit? 核转运:氧化应激信号通路的开关?

Journal of signal transduction Pub Date : 2012-01-01 Epub Date: 2011-10-15 DOI: 10.1155/2012/208650

Mohamed Kodiha, Ursula Stochaj

引用次数: 62

Oxidative Stress Induced by MnSOD-p53 Interaction: Pro- or Anti-Tumorigenic? MnSOD-p53相互作用诱导的氧化应激:促肿瘤还是抗肿瘤?

Journal of signal transduction Pub Date : 2012-01-01 Epub Date: 2011-10-05 DOI: 10.1155/2012/101465

Delira Robbins, Yunfeng Zhao

{"title":"Oxidative Stress Induced by MnSOD-p53 Interaction: Pro- or Anti-Tumorigenic?","authors":"Delira Robbins, Yunfeng Zhao","doi":"10.1155/2012/101465","DOIUrl":"https://doi.org/10.1155/2012/101465","url":null,"abstract":"The formation of reactive oxygen species (ROS) is a result of incomplete reduction of molecular oxygen during cellular metabolism. Although ROS has been shown to act as signaling molecules, it is known that these reactive molecules can act as prooxidants causing damage to DNA, proteins, and lipids, which over time can lead to disease propagation and ultimately cell death. Thus, restoring the protective antioxidant capacity of the cell has become an important target in therapeutic intervention. In addition, a clearer understanding of the disease stage and molecular events that contribute to ROS generation during tumor promotion can lead to novel approaches to enhance target specificity in cancer progression. This paper will focus on not only the traditional routes of ROS generation, but also on new mechanisms via the tumor suppressor p53 and the interaction between p53 and MnSOD, the primary antioxidant enzyme in mitochondria. In addition, the potential consequences of the p53-MnSOD interaction have also been discussed. Lastly, we have highlighted clinical implications of targeting the p53-MnSOD interaction and discussed recent therapeutic mechanisms utilized to modulate both p53 and MnSOD as a method of tumor suppression.","PeriodicalId":89176,"journal":{"name":"Journal of signal transduction","volume":"2012 ","pages":"101465"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/101465","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30213885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 39

Mitochondrial Oxidative Stress due to Complex I Dysfunction Promotes Fibroblast Activation and Melanoma Cell Invasiveness. 复合体I功能障碍引起的线粒体氧化应激促进成纤维细胞活化和黑色素瘤细胞侵袭。

Journal of signal transduction Pub Date : 2012-01-01 Epub Date: 2012-01-04 DOI: 10.1155/2012/684592

Maria Letizia Taddei, Elisa Giannoni, Giovanni Raugei, Salvatore Scacco, Anna Maria Sardanelli, Sergio Papa, Paola Chiarugi

{"title":"Mitochondrial Oxidative Stress due to Complex I Dysfunction Promotes Fibroblast Activation and Melanoma Cell Invasiveness.","authors":"Maria Letizia Taddei, Elisa Giannoni, Giovanni Raugei, Salvatore Scacco, Anna Maria Sardanelli, Sergio Papa, Paola Chiarugi","doi":"10.1155/2012/684592","DOIUrl":"https://doi.org/10.1155/2012/684592","url":null,"abstract":"Increased ROS (cellular reactive oxygen species) are characteristic of both fibrosis and tumour development. ROS induce the trans-differentiation to myofibroblasts, the activated form of fibroblasts able to promote cancer progression. Here, we report the role of ROS produced in response to dysfunctions of mitochondrial complex I, in fibroblast activation and in tumour progression. We studied human fibroblasts with mitochondrial dysfunctions of complex I, leading to hyperproduction of ROS. We demonstrated that ROS level produced by the mutated fibroblasts correlates with their activation. The increase of ROS in these cells provides a greater ability to remodel the extracellular matrix leading to an increased motility and invasiveness. Furthermore, we evidentiated that in hypoxic conditions these fibroblasts cause HIF-1α stabilization and promote a proinvasive phenotype of human melanoma cells through secretion of cytokines. These data suggest a possible role of deregulated mitochondrial ROS production in fibrosis evolution as well as in cancer progression and invasion.","PeriodicalId":89176,"journal":{"name":"Journal of signal transduction","volume":"2012 ","pages":"684592"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/684592","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30410424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 63

RGD-Dependent Epithelial Cell-Matrix Interactions in the Human Intestinal Crypt. 人肠隐窝中rgd依赖性上皮细胞-基质相互作用。

Journal of signal transduction Pub Date : 2012-01-01 Epub Date: 2012-09-05 DOI: 10.1155/2012/248759

Yannick D Benoit, Jean-François Groulx, David Gagné, Jean-François Beaulieu

引用次数: 46

NPM-ALK: The Prototypic Member of a Family of Oncogenic Fusion Tyrosine Kinases. NPM-ALK:一个致癌融合酪氨酸激酶家族的原型成员。

Journal of signal transduction Pub Date : 2012-01-01 Epub Date: 2012-07-18 DOI: 10.1155/2012/123253

Joel D Pearson, Jason K H Lee, Julinor T C Bacani, Raymond Lai, Robert J Ingham

{"title":"NPM-ALK: The Prototypic Member of a Family of Oncogenic Fusion Tyrosine Kinases.","authors":"Joel D Pearson, Jason K H Lee, Julinor T C Bacani, Raymond Lai, Robert J Ingham","doi":"10.1155/2012/123253","DOIUrl":"https://doi.org/10.1155/2012/123253","url":null,"abstract":"Anaplastic lymphoma kinase (ALK) was first identified in 1994 with the discovery that the gene encoding for this kinase was involved in the t(2;5)(p23;q35) chromosomal translocation observed in a subset of anaplastic large cell lymphoma (ALCL). The NPM-ALK fusion protein generated by this translocation is a constitutively active tyrosine kinase, and much research has focused on characterizing the signalling pathways and cellular activities this oncoprotein regulates in ALCL. We now know about the existence of nearly 20 distinct ALK translocation partners, and the fusion proteins resulting from these translocations play a critical role in the pathogenesis of a variety of cancers including subsets of large B-cell lymphomas, nonsmall cell lung carcinomas, and inflammatory myofibroblastic tumours. Moreover, the inhibition of ALK has been shown to be an effective treatment strategy in some of these malignancies. In this paper we will highlight malignancies where ALK translocations have been identified and discuss why ALK fusion proteins are constitutively active tyrosine kinases. Finally, using ALCL as an example, we will examine three key signalling pathways activated by NPM-ALK that contribute to proliferation and survival in ALCL.","PeriodicalId":89176,"journal":{"name":"Journal of signal transduction","volume":"2012 ","pages":"123253"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/123253","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30803619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 39

Angiogenic signalling pathways altered in gliomas: selection mechanisms for more aggressive neoplastic subpopulations with invasive phenotype. 胶质瘤中血管生成信号通路的改变:具有侵袭性表型的更具侵袭性的肿瘤亚群的选择机制。

Journal of signal transduction Pub Date : 2012-01-01 Epub Date: 2012-07-17 DOI: 10.1155/2012/597915

Susana Bulnes, Harkaitz Bengoetxea, Naiara Ortuzar, Enrike G Argandoña, Alvaro Garcia-Blanco, Irantzu Rico-Barrio, José V Lafuente

{"title":"Angiogenic signalling pathways altered in gliomas: selection mechanisms for more aggressive neoplastic subpopulations with invasive phenotype.","authors":"Susana Bulnes, Harkaitz Bengoetxea, Naiara Ortuzar, Enrike G Argandoña, Alvaro Garcia-Blanco, Irantzu Rico-Barrio, José V Lafuente","doi":"10.1155/2012/597915","DOIUrl":"https://doi.org/10.1155/2012/597915","url":null,"abstract":"The angiogenesis process is a key event for glioma survival, malignancy and growth. The start of angiogenesis is mediated by a cascade of intratumoural events: alteration of the microvasculature network; a hypoxic microenvironment; adaptation of neoplastic cells and synthesis of pro-angiogenic factors. Due to a chaotic blood flow, a consequence of an aberrant microvasculature, tissue hypoxia phenomena are induced. Hypoxia inducible factor 1 is a major regulator in glioma invasiveness and angiogenesis. Clones of neoplastic cells with stem cell characteristics are selected by HIF-1. These cells, called \"glioma stem cells\" induce the synthesis of vascular endothelial growth factor. This factor is a pivotal mediator of angiogenesis. To elucidate the role of these angiogenic mediators during glioma growth, we have used a rat endogenous glioma model. Gliomas induced by prenatal ENU administration allowed us to study angiogenic events from early to advanced tumour stages. Events such as microvascular aberrations, hypoxia, GSC selection and VEGF synthesis may be studied in depth. Our data showed that for the treatment of gliomas, developing anti-angiogenic therapies could be aimed at GSCs, HIF-1 or VEGF. The ENU-glioma model can be considered to be a useful option to check novel designs of these treatment strategies.","PeriodicalId":89176,"journal":{"name":"Journal of signal transduction","volume":"2012 ","pages":"597915"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/597915","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30803620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 27

Prolactin and dexamethasone regulate second messenger-stimulated cl(-) secretion in mammary epithelia. 催乳素和地塞米松调节乳腺上皮第二信使刺激的cl(-)分泌。

Journal of signal transduction Pub Date : 2012-01-01 Epub Date: 2012-07-25 DOI: 10.1155/2012/192142

Utchariya Anantamongkol, Mei Ao, Jayashree Sarathy Nee Venkatasubramanian, Y Sangeeta Devi, Nateetip Krishnamra, Mrinalini C Rao

{"title":"Prolactin and dexamethasone regulate second messenger-stimulated cl(-) secretion in mammary epithelia.","authors":"Utchariya Anantamongkol, Mei Ao, Jayashree Sarathy Nee Venkatasubramanian, Y Sangeeta Devi, Nateetip Krishnamra, Mrinalini C Rao","doi":"10.1155/2012/192142","DOIUrl":"https://doi.org/10.1155/2012/192142","url":null,"abstract":"Mammary gland ion transport is essential for lactation and is regulated by prolactin and glucocorticoids. This study delineates the roles of prolactin receptors (PRLR) and long-term prolactin and dexamethasone (P-D)-mediation of [Ca(2+)](i) and Cl(-) transport in HC-11 cells. P-D (24 h) suppressed ATP-induced [Ca(2+)](i). This may be due to decreased Ca(2+) entry since P-D decreased transient receptor potential channel 3 (TRPC3) but not secretory pathway Ca(2+)-ATPase 2 (SPCA2) mRNA. ATP increased Cl(-) transport, measured by iodide (I(-)) efflux, in control and P-D-treated cells. P-D enhanced I(-) efflux response to cAMP secretagogues without altering Cl(-) channels or NKCC cotransporter expression. HC-11 cells contain only the long form of PRLR (PRLR-L). Since the short isoform, PRLR-S, is mammopoietic, we determined if transfecting PRLR-S (rs) altered PRLR-L-mediated Ca(2+) and Cl(-) transport. Untreated rs cells showed an attenuated [Ca(2+)](i) response to ATP with no further response to P-D, in contrast to vector-transfected (vtc) controls. P-D inhibited TRPC3 in rs and vtc cells but increased SPCA2 only in rs cells. As in wild-type, cAMP-stimulated Cl(-) transport, in P-D-treated vtc and rs cells. In summary, 24 h P-D acts via PRLR-L to attenuate ATP-induced [Ca(2+)](i) and increase cAMP-activated Cl(-) transport. PRLR-S fine-tunes these responses underscoring its mammopoietic action.","PeriodicalId":89176,"journal":{"name":"Journal of signal transduction","volume":"2012 ","pages":"192142"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/192142","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30830063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

MAP Kinases and Prostate Cancer. MAP激酶与前列腺癌。

Journal of signal transduction Pub Date : 2012-01-01 Epub Date: 2011-10-20 DOI: 10.1155/2012/169170

Gonzalo Rodríguez-Berriguete, Benito Fraile, Pilar Martínez-Onsurbe, Gabriel Olmedilla, Ricardo Paniagua, Mar Royuela

引用次数: 126

The Concept of Divergent Targeting through the Activation and Inhibition of Receptors as a Novel Chemotherapeutic Strategy: Signaling Responses to Strong DNA-Reactive Combinatorial Mimicries. 通过激活和抑制受体的发散靶向概念作为一种新的化疗策略:对强dna反应性组合模仿的信号反应。

Journal of signal transduction Pub Date : 2012-01-01 Epub Date: 2012-03-07 DOI: 10.1155/2012/282050

Heather L Watt, Zakaria Rachid, Bertrand J Jean-Claude

{"title":"The Concept of Divergent Targeting through the Activation and Inhibition of Receptors as a Novel Chemotherapeutic Strategy: Signaling Responses to Strong DNA-Reactive Combinatorial Mimicries.","authors":"Heather L Watt, Zakaria Rachid, Bertrand J Jean-Claude","doi":"10.1155/2012/282050","DOIUrl":"https://doi.org/10.1155/2012/282050","url":null,"abstract":"Recently, we reported the combination of multitargeted ErbB1 inhibitor-DNA damage combi-molecules with OCT in order to downregulate ErbB1 and activate SSTRs. Absence of translation to cell kill was believed to be partially due to insufficient ErbB1 blockage and DNA damage. In this study, we evaluated cell response to molecules that damage DNA more aggressively and induce stronger attenuation of ErbB1 phosphorylation. We used three cell lines expressing low levels (U87MG) or transfected to overexpress wildtype (U87/EGFR) or a variant (U87/EGFRvIII) of ErbB1. The results showed that Iressa ± HN2 and the combi-molecules, ZRBA4 and ZR2003, significantly blocked ErbB1 phosphorylation in U87MG cells. Addition of OCT significantly altered cell cycle distribution. Analysis of the DNA damage response pathway revealed strong upregulation of p53 by HN2 and the combi-molecules. Apoptosis was only induced by a 48 h exposure to HN2. All other treatments resulted in cell necrosis. This is in agreement with Akt-Bad pathway activation and survivin upregulation. Despite strong DNA damaging properties and downregulation of ErbB1 phosphorylation by these molecules, the strongest effect of SSTR activation was on cell cycle distribution. Therefore, any enhanced antiproliferative effects of combining ErbB1 inhibition with SSTR activation must be addressed in the context of cell cycle arrest.","PeriodicalId":89176,"journal":{"name":"Journal of signal transduction","volume":" ","pages":"282050"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/282050","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40171906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4