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      Epithelial protein lost in neoplasm (EPLIN): Beyond a tumor suppressor

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          Abstract

          The majority of cancer-related deaths are caused by tumor recurrence, metastasis and therapeutic resistance. During the late stages of tumor progression, multiple factors are involved, including the downregulation and/or loss of function of metastasis suppressors. Epithelial protein lost in neoplasm (EPLIN), an actin-binding protein, was initially identified as a putative tumor suppressor that is frequently downregulated in epithelial tumors. Recent evidence indicates that EPLIN may negatively regulate epithelia-to-mesenchymal transition (EMT), a crucial process by which cancer cells acquire invasive capabilities and therapeutic resistance. Importantly, downregulation of EPLIN is associated with clinical metastasis in a variety of solid tumors, suggesting that EPLIN could be a suppressor of metastasis. In this review, I will discuss the regulation and function of EPLIN in human cancer cells and explore the clinical significance of EPLIN in metastatic disease.

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          Most cited references26

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          Gene expression profiling identifies clinically relevant subtypes of prostate cancer.

          Prostate cancer, a leading cause of cancer death, displays a broad range of clinical behavior from relatively indolent to aggressive metastatic disease. To explore potential molecular variation underlying this clinical heterogeneity, we profiled gene expression in 62 primary prostate tumors, as well as 41 normal prostate specimens and nine lymph node metastases, using cDNA microarrays containing approximately 26,000 genes. Unsupervised hierarchical clustering readily distinguished tumors from normal samples, and further identified three subclasses of prostate tumors based on distinct patterns of gene expression. High-grade and advanced stage tumors, as well as tumors associated with recurrence, were disproportionately represented among two of the three subtypes, one of which also included most lymph node metastases. To further characterize the clinical relevance of tumor subtypes, we evaluated as surrogate markers two genes differentially expressed among tumor subgroups by using immunohistochemistry on tissue microarrays representing an independent set of 225 prostate tumors. Positive staining for MUC1, a gene highly expressed in the subgroups with "aggressive" clinicopathological features, was associated with an elevated risk of recurrence (P = 0.003), whereas strong staining for AZGP1, a gene highly expressed in the other subgroup, was associated with a decreased risk of recurrence (P = 0.0008). In multivariate analysis, MUC1 and AZGP1 staining were strong predictors of tumor recurrence independent of tumor grade, stage, and preoperative prostate-specific antigen levels. Our results suggest that prostate tumors can be usefully classified according to their gene expression patterns, and these tumor subtypes may provide a basis for improved prognostication and treatment stratification.
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            Gene expression alterations in prostate cancer predicting tumor aggression and preceding development of malignancy.

            The incidence of prostate cancer is frequent, occurring in almost one-third of men older than 45 years. Only a fraction of the cases reach the stages displaying clinical significance. Despite the advances in our understanding of prostate carcinogenesis and disease progression, our knowledge of this disease is still fragmented. Identification of the genes and patterns of gene expression will provide a more cohesive picture of prostate cancer biology. In this study, we performed a comprehensive gene expression analysis on 152 human samples including prostate cancer tissues, prostate tissues adjacent to tumor, and organ donor prostate tissues, obtained from men of various ages, using the Affymetrix (Santa Clara, CA) U95a, U95b, and U95c chip sets (37,777 genes and expression sequence tags). Our results confirm an alteration of gene expression in prostate cancer when comparing with nontumor adjacent prostate tissues. However, our study also indicates that the gene expression pattern in tissues adjacent to cancer is so substantially altered that it resembles a cancer field effect. We also found that gene expression patterns can be used to predict the aggressiveness of prostate cancer using a novel model.
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              Epithelial junctions and Rho family GTPases: the zonular signalosome

              The establishment and maintenance of epithelial cell-cell junctions is crucially important to regulate adhesion, apico-basal polarity and motility of epithelial cells, and ultimately controls the architecture and physiology of epithelial organs. Junctions are supported, shaped and regulated by cytoskeletal filaments, whose dynamic organization and contractility are finely tuned by GTPases of the Rho family, primarily RhoA, Rac1 and Cdc42. Recent research has identified new molecular mechanisms underlying the cross-talk between these GTPases and epithelial junctions. Here we briefly summarize the current knowledge about the organization, molecular evolution and cytoskeletal anchoring of cell-cell junctions, and we comment on the most recent advances in the characterization of the interactions between Rho GTPases and junctional proteins, and their consequences with regards to junction assembly and regulation of cell behavior in vertebrate model systems. The concept of “zonular signalosome” is proposed, which highlights the close functional relationship between proteins of zonular junctions (zonulae occludentes and adhaerentes) and the control of cytoskeletal organization and signaling through Rho GTPases, transcription factors, and their effectors.
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                Author and article information

                Contributors
                Journal
                Genes Dis
                Genes Dis
                Genes & Diseases
                Chongqing Medical University
                2352-3042
                01 April 2017
                June 2017
                01 April 2017
                : 4
                : 2
                : 100-107
                Affiliations
                [a ]Georgia Cancer Center and Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA, USA
                [b ]MetCure Therapeutics LLC, Atlanta, GA, USA
                Author notes
                []Corresponding author. Georgia Cancer Center and Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA, USA. dwu@ 123456augusta.edu
                Article
                S2352-3042(17)30025-9
                10.1016/j.gendis.2017.03.002
                6136588
                30258911
                9860afad-a652-4b70-a493-90c82f79eaf6
                Copyright © 2017, Chongqing Medical University. Production and hosting by Elsevier B.V.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 13 December 2016
                : 25 March 2017
                Categories
                Article

                actin cytoskeleton,chemoresistance,epithelial-to-mesenchymal transition,eplin,metastasis suppressor,tumor suppressor

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