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      Survivin and Tumorigenesis: Molecular Mechanisms and Therapeutic Strategies

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          Abstract

          Survivin is the smallest member of the inhibitor of apoptosis protein family, which has key roles in regulating cell division and inhibiting apoptosis by blocking caspase activation. Survivin is highly expressed in most human cancers, such as lung, pancreatic and breast cancers, relative to normal tissues. Aberrant survivin expression is associated with tumor cell proliferation, progression, angiogenesis, therapeutic resistance, and poor prognosis. Studies on the underlying molecular mechanisms indicate that survivin is involved in the regulation of cytokinesis and cell cycle progression, as well as participates in a variety of signaling pathways such as the p53, Wnt, hypoxia, transforming growth factor, and Notch signaling pathways. In this review, recent progress in understanding the molecular basis of survivin is discussed. Therapeutic strategies targeting survivin in preclinical studies are also briefly summarized.

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          Most cited references74

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          Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy.

          Apoptosis or programmed cell death is a key regulator of physiological growth control and regulation of tissue homeostasis. One of the most important advances in cancer research in recent years is the recognition that cell death mostly by apoptosis is crucially involved in the regulation of tumor formation and also critically determines treatment response. Killing of tumor cells by most anticancer strategies currently used in clinical oncology, for example, chemotherapy, gamma-irradiation, suicide gene therapy or immunotherapy, has been linked to activation of apoptosis signal transduction pathways in cancer cells such as the intrinsic and/or extrinsic pathway. Thus, failure to undergo apoptosis may result in treatment resistance. Understanding the molecular events that regulate apoptosis in response to anticancer chemotherapy, and how cancer cells evade apoptotic death, provides novel opportunities for a more rational approach to develop molecular-targeted therapies for combating cancer.
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            Is Open Access

            Apoptosis, autophagy, necroptosis, and cancer metastasis

            Metastasis is a crucial hallmark of cancer progression, which involves numerous factors including the degradation of the extracellular matrix (ECM), the epithelial-to-mesenchymal transition (EMT), tumor angiogenesis, the development of an inflammatory tumor microenvironment, and defects in programmed cell death. Programmed cell death, such as apoptosis, autophagy, and necroptosis, plays crucial roles in metastatic processes. Malignant tumor cells must overcome these various forms of cell death to metastasize. This review summarizes the recent advances in the understanding of the mechanisms by which key regulators of apoptosis, autophagy, and necroptosis participate in cancer metastasis and discusses the crosstalk between apoptosis, autophagy, and necroptosis involved in the regulation of cancer metastasis.
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              Control of apoptosis by p53.

              The p53 tumor suppressor acts to integrate multiple stress signals into a series of diverse antiproliferative responses. One of the most important p53 functions is its ability to activate apoptosis, and disruption of this process can promote tumor progression and chemoresistance. p53 apparently promotes apoptosis through transcription-dependent and -independent mechanisms that act in concert to ensure that the cell death program proceeds efficiently. Moreover, the apoptotic activity of p53 is tightly controlled, and is influenced by a series of quantitative and qualitative events that influence the outcome of p53 activation. Interestingly, other p53 family members can also promote apoptosis, either in parallel or in concert with p53. Although incomplete, our current understanding of p53 illustrates how apoptosis can be integrated into a larger tumor suppressor network controlled by different signals, environmental factors, and cell type. Understanding this network in more detail will provide insights into cancer and other diseases, and will identify strategies to improve their therapeutic treatment.
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                Author and article information

                Journal
                J Cancer
                J Cancer
                jca
                Journal of Cancer
                Ivyspring International Publisher (Sydney )
                1837-9664
                2016
                10 January 2016
                : 7
                : 3
                : 314-323
                Affiliations
                1. Hong-Hui Hospital, Xi'an Jiaotong University, College of Medicine, Xi'an, Shaanxi, China, 710054
                2. Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO, USA, 80045
                Author notes

                * These authors contribute equally to this work.

                Competing Interests: The authors declare no conflict of interest. This article does not contain any studies with human or animal subjects performed by the authors.

                Article
                jcav07p0314
                10.7150/jca.13332
                4747886
                26918045
                9490d87e-6245-4a44-8866-79a5c02ce22a
                © Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. See http://ivyspring.com/terms for terms and conditions.
                History
                : 24 July 2015
                : 25 November 2015
                Categories
                Review

                Oncology & Radiotherapy
                survivin,apoptosis,cell cycle,cancer,therapy
                Oncology & Radiotherapy
                survivin, apoptosis, cell cycle, cancer, therapy

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