STAT proteins: From normal control of cellular events to tumorigenesis

Authors

  • Valentina Calò,

    1. Section of Molecular Oncology, Department of Oncology, Regional Reference Center for the Biomolecular Characterization of Neoplasms and Genetic Screening of Hereditary Tumors, University of Palermo, Palermo, Italy
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  • Manuela Migliavacca,

    1. Section of Histology, Department of Experimental Medicine; University of Palermo, Palermo, Italy
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  • Viviana Bazan,

    1. Section of Molecular Oncology, Department of Oncology, Regional Reference Center for the Biomolecular Characterization of Neoplasms and Genetic Screening of Hereditary Tumors, University of Palermo, Palermo, Italy
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  • Marcella Macaluso,

    1. Section of Molecular Oncology, Department of Oncology, Regional Reference Center for the Biomolecular Characterization of Neoplasms and Genetic Screening of Hereditary Tumors, University of Palermo, Palermo, Italy
    2. Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, Philadelphia
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  • Maria Buscemi,

    1. Section of Histology, Department of Experimental Medicine; University of Palermo, Palermo, Italy
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  • Nicola Gebbia,

    1. Section of Medical Oncology, Department of Oncology, Regional Reference Center for the Biomolecular Characterization of Neoplasms and Genetic Screening of Hereditary Tumors, University of Palermo, Palermo, Italy
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  • Antonio Russo

    Corresponding author
    1. Section of Molecular Oncology, Department of Oncology, Regional Reference Center for the Biomolecular Characterization of Neoplasms and Genetic Screening of Hereditary Tumors, University of Palermo, Palermo, Italy
    • Via Veneto 5, 90144 Palermo, Italy.
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  • The authorship is shared equally by Valentina Calò and Manuela Migliavacca, and their names are listed in alphabetical order.

Abstract

Signal transducers and activators of transcription (STAT) proteins comprise a family of transcription factors latent in the cytoplasm that participate in normal cellular events, such as differentiation, proliferation, cell survival, apoptosis, and angiogenesis following cytokine, growth factor, and hormone signaling. STATs are activated by tyrosine phosphorylation, which is normally a transient and tightly regulates process. Nevertheless, several constitutively activated STATs have been observed in a wide number of human cancer cell lines and primary tumors, including blood malignancies and solid neoplasias. STATs can be divided into two groups according to their specific functions. One is made up of STAT2, STAT4, and STAT6, which are activated by a small number of cytokines and play a distinct role in the development of T-cells and in IFNγ signaling. The other group includes STAT1, STAT3, and STAT5, activated in different tissues by means of a series of ligands and involved in IFN signaling, development of the mammary gland, response to GH, and embriogenesis. This latter group of STATS plays an important role in controlling cell-cycle progression and apoptosis and thus contributes to oncogenesis. Although an increased expression of STAT1 has been observed in many human neoplasias, this molecule can be considered a potential tumor suppressor, since it plays an important role in growth arrest and in promoting apoptosis. On the other hand, STAT3 and 5 are considered as oncogenes, since they bring about the activation of cyclin D1, c-Myc, and bcl-xl expression, and are involved in promoting cell-cycle progression, cellular transformation, and in preventing apoptosis. J. Cell. Physiol. 197: 157–168, 2003© 2003 Wiley-Liss, Inc.

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