The Multifaced Role of STAT3 in Cancer and Its Implication for Anticancer Therapy
Signal transducer and activator of transcription (STAT) 3 is one of the most complex regulators of transcription. Constitutive activation of STAT3 has been reported in many types of tumors and depends on mechanisms such as hyperactivation of receptors for pro-oncogenic cytokines and growth factors,...
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| Format: | Article |
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MDPI AG
2021-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/2/603 |
| _version_ | 1797414008508121088 |
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| author | Manlio Tolomeo Antonio Cascio |
| author_facet | Manlio Tolomeo Antonio Cascio |
| author_sort | Manlio Tolomeo |
| collection | DOAJ |
| description | Signal transducer and activator of transcription (STAT) 3 is one of the most complex regulators of transcription. Constitutive activation of STAT3 has been reported in many types of tumors and depends on mechanisms such as hyperactivation of receptors for pro-oncogenic cytokines and growth factors, loss of negative regulation, and excessive cytokine stimulation. In contrast, somatic STAT3 mutations are less frequent in cancer. Several oncogenic targets of STAT3 have been recently identified such as c-myc, c-Jun, PLK-1, Pim1/2, Bcl-2, VEGF, bFGF, and Cten, and inhibitors of STAT3 have been developed for cancer prevention and treatment. However, despite the oncogenic role of STAT3 having been widely demonstrated, an increasing amount of data indicate that STAT3 functions are multifaced and not easy to classify. In fact, the specific cellular role of STAT3 seems to be determined by the integration of multiple signals, by the oncogenic environment, and by the alternative splicing into two distinct isoforms, STAT3α and STAT3β. On the basis of these different conditions, STAT3 can act both as a potent tumor promoter or tumor suppressor factor. This implies that the therapies based on STAT3 modulators should be performed considering the pleiotropic functions of this transcription factor and tailored to the specific tumor type. |
| first_indexed | 2024-03-09T05:26:53Z |
| format | Article |
| id | doaj.art-01518f0f028b4cfa8b236aee57ab50aa |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T05:26:53Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-01518f0f028b4cfa8b236aee57ab50aa2023-12-03T12:35:41ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-01-0122260310.3390/ijms22020603The Multifaced Role of STAT3 in Cancer and Its Implication for Anticancer TherapyManlio Tolomeo0Antonio Cascio1Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties, University of Palermo, via del Vespro 129, 90127 Palermo, ItalyDepartment of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties, University of Palermo, via del Vespro 129, 90127 Palermo, ItalySignal transducer and activator of transcription (STAT) 3 is one of the most complex regulators of transcription. Constitutive activation of STAT3 has been reported in many types of tumors and depends on mechanisms such as hyperactivation of receptors for pro-oncogenic cytokines and growth factors, loss of negative regulation, and excessive cytokine stimulation. In contrast, somatic STAT3 mutations are less frequent in cancer. Several oncogenic targets of STAT3 have been recently identified such as c-myc, c-Jun, PLK-1, Pim1/2, Bcl-2, VEGF, bFGF, and Cten, and inhibitors of STAT3 have been developed for cancer prevention and treatment. However, despite the oncogenic role of STAT3 having been widely demonstrated, an increasing amount of data indicate that STAT3 functions are multifaced and not easy to classify. In fact, the specific cellular role of STAT3 seems to be determined by the integration of multiple signals, by the oncogenic environment, and by the alternative splicing into two distinct isoforms, STAT3α and STAT3β. On the basis of these different conditions, STAT3 can act both as a potent tumor promoter or tumor suppressor factor. This implies that the therapies based on STAT3 modulators should be performed considering the pleiotropic functions of this transcription factor and tailored to the specific tumor type.https://www.mdpi.com/1422-0067/22/2/603STAT3cancertumor promotertumor suppressor |
| spellingShingle | Manlio Tolomeo Antonio Cascio The Multifaced Role of STAT3 in Cancer and Its Implication for Anticancer Therapy International Journal of Molecular Sciences STAT3 cancer tumor promoter tumor suppressor |
| title | The Multifaced Role of STAT3 in Cancer and Its Implication for Anticancer Therapy |
| title_full | The Multifaced Role of STAT3 in Cancer and Its Implication for Anticancer Therapy |
| title_fullStr | The Multifaced Role of STAT3 in Cancer and Its Implication for Anticancer Therapy |
| title_full_unstemmed | The Multifaced Role of STAT3 in Cancer and Its Implication for Anticancer Therapy |
| title_short | The Multifaced Role of STAT3 in Cancer and Its Implication for Anticancer Therapy |
| title_sort | multifaced role of stat3 in cancer and its implication for anticancer therapy |
| topic | STAT3 cancer tumor promoter tumor suppressor |
| url | https://www.mdpi.com/1422-0067/22/2/603 |
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