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      Tyrosine kinase LYN is an oncotarget in human cervical cancer: A quantitative proteomic based study

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          Abstract

          Cervical cancer is one of the most common malignant tumor in women. The mechanisms of cervical cancer are intricate and have not been fully understood. Therefore, we employed iTRAQ to obtain novel proteins profile which participates in the tumor oncogenesis of cervical cancer. 3300 proteins were identified aberrantly expressed in cervical cancer, and western bolt was performed to validate the results of iTRAQ. Then, we selected LYN for further study. Immunohistochemistry identified that LYN expression was significantly increased in cervical cancer tissues than that in cancer adjacent normal cervical tissues and normal cervical tissues. The increased LYN expression was significantly correlated with cancer differentiation and FIGO stage. Silencing LYN inhibited cell proliferation, migration and invasion, conversely, overexpression LYN promoted cell proliferation, migration and invasion. In terms of mechanism, LYN could also promote cervical cancer cells metastasis through activating IL-6/STAT3 pathway. In vivo study, overexpression LYN promoted tumor growth, meanwhile knockdown LYN inhibited tumor growth. These results indicate that LYN tyrosine kinase is an oncogenic gene and can serve as a novel target for cervical cancer research and therapy.

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          Most cited references21

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          Src family kinases, key regulators of signal transduction.

          The Src family of protein tyrosine kinases (SFKs) plays key roles in regulating signal transduction by a diverse set of cell surface receptors in the context of a variety of cellular environments. SFKs have evolved many ingenious molecular strategies to couple receptors with the cytoplasmic signaling machinery. The contributions to this issue of ONCOGENE describe how this machinery regulates fundamental cellular processes, including cell growth, differentiation, cell shape, migration and survival, and specialized cell signals. The pleiotropic functions of Src and Src family members underscore the importance of these kinases and explain why many of the members of this family have been identified as cellular oncogenes. In this volume, we have attempted to provide the reader with an overview of the current understanding of the function of Src family kinases in the regulation of selected cellular signaling pathways.
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            An insight into iTRAQ: where do we stand now?

            The iTRAQ (isobaric tags for relative and absolute quantification) technique is widely employed in proteomic workflows requiring relative quantification. Here, we review the iTRAQ literature; in particular, we focus on iTRAQ usage in relation to other commonly used quantitative techniques e.g. stable isotope labelling in culture (SILAC), label-free methods and selected reaction monitoring (SRM). As a result, we identify several issues arising with respect to iTRAQ. Perhaps frustratingly, iTRAQ's attractiveness has been undermined by a number of technical and analytical limitations: it may not be truly quantitative, as the changes in abundance reported will generally be underestimated. We discuss weaknesses and strengths of iTRAQ as a methodology for relative quantification in the light of this and other technical issues. We focus on technical developments targeted at iTRAQ accuracy and precision, use of 4-plex over 8-plex reagents and application of iTRAQ to post-translational modification (PTM) workflows. We also discuss iTRAQ in relation to label-free approaches, to which iTRAQ is losing ground.
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              Tyrosine kinase B receptor and BDNF expression in ovarian cancers - Effect on cell migration, angiogenesis and clinical outcome.

              In this report, we demonstrated that overexpression of tropomyosin-related kinase B (TrkB) was associated with shorter survival in ovarian cancer patients. Brain-derived neurotrophic factor (BDNF), the TrkB ligand, induced activation (phosphorylation) of TrkB in a dose dependent manner. Besides demonstrating the effect of BDNF/TrkB pathway in enhancing cancer cell migration and invasion but inhibiting apoptosis, we also report for the first time that exogenous hepatocyte growth factor induced TrkB expression at both mRNA and protein levels as well as phosphorylation. Our findings suggest that BDNF/TrkB pathway is important in ovarian carcinogenesis and TrkB may be a potential therapeutic target for ovarian cancer.
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                Author and article information

                Journal
                Oncotarget
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                15 November 2016
                26 September 2016
                : 7
                : 46
                : 75468-75481
                Affiliations
                1 Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, PR China
                2 Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, PR China
                Author notes
                Correspondence to: Li-Na Hu, cqhulina@ 123456126.com
                Article
                12258
                10.18632/oncotarget.12258
                5342753
                27690342
                1829df99-07e2-4d49-97ef-0696f3f4fe73
                Copyright: © 2016 Liu et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 28 March 2016
                : 2 September 2016
                Categories
                Research Paper

                Oncology & Radiotherapy
                itraq,cervical cancer,lyn,stat3,il-6
                Oncology & Radiotherapy
                itraq, cervical cancer, lyn, stat3, il-6

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