Balancing STAT Activity as a Therapeutic Strategy
Driven by dysregulated IL-6 family member cytokine signaling in the tumor microenvironment (TME), aberrant signal transducer and activator of transcription (STAT3) and (STAT5) activation have been identified as key contributors to tumorigenesis. Following transformation, persistent STAT3 activation...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-11-01
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| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/11/11/1716 |
| _version_ | 1797763204435148800 |
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| author | Kelsey L. Polak Noah M. Chernosky Jacob M. Smigiel Ilaria Tamagno Mark W. Jackson |
| author_facet | Kelsey L. Polak Noah M. Chernosky Jacob M. Smigiel Ilaria Tamagno Mark W. Jackson |
| author_sort | Kelsey L. Polak |
| collection | DOAJ |
| description | Driven by dysregulated IL-6 family member cytokine signaling in the tumor microenvironment (TME), aberrant signal transducer and activator of transcription (STAT3) and (STAT5) activation have been identified as key contributors to tumorigenesis. Following transformation, persistent STAT3 activation drives the emergence of mesenchymal/cancer-stem cell (CSC) properties, important determinants of metastatic potential and therapy failure. Moreover, STAT3 signaling within tumor-associated macrophages and neutrophils drives secretion of factors that facilitate metastasis and suppress immune cell function. Persistent STAT5 activation is responsible for cancer cell maintenance through suppression of apoptosis and tumor suppressor signaling. Furthermore, STAT5-mediated CD4+/CD25+ regulatory T cells (T<sub>regs</sub>) have been implicated in suppression of immunosurveillance. We discuss these roles for STAT3 and STAT5, and weigh the attractiveness of different modes of targeting each cancer therapy. Moreover, we discuss how anti-tumorigenic STATs, including STAT1 and STAT2, may be leveraged to suppress the pro-tumorigenic functions of STAT3/STAT5 signaling. |
| first_indexed | 2024-03-12T19:38:12Z |
| format | Article |
| id | doaj.art-38a71866c53b4a809fb902577535bda5 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T19:38:12Z |
| publishDate | 2019-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-38a71866c53b4a809fb902577535bda52023-08-02T03:58:59ZengMDPI AGCancers2072-66942019-11-011111171610.3390/cancers11111716cancers11111716Balancing STAT Activity as a Therapeutic StrategyKelsey L. Polak0Noah M. Chernosky1Jacob M. Smigiel2Ilaria Tamagno3Mark W. Jackson4Department of Pathology, Case Western Reserve University, School of Medicine, Cleveland, OH 44106, USADepartment of Pathology, Case Western Reserve University, School of Medicine, Cleveland, OH 44106, USADepartment of Pathology, Case Western Reserve University, School of Medicine, Cleveland, OH 44106, USADepartment of Pathology, Case Western Reserve University, School of Medicine, Cleveland, OH 44106, USADepartment of Pathology, Case Western Reserve University, School of Medicine, Cleveland, OH 44106, USADriven by dysregulated IL-6 family member cytokine signaling in the tumor microenvironment (TME), aberrant signal transducer and activator of transcription (STAT3) and (STAT5) activation have been identified as key contributors to tumorigenesis. Following transformation, persistent STAT3 activation drives the emergence of mesenchymal/cancer-stem cell (CSC) properties, important determinants of metastatic potential and therapy failure. Moreover, STAT3 signaling within tumor-associated macrophages and neutrophils drives secretion of factors that facilitate metastasis and suppress immune cell function. Persistent STAT5 activation is responsible for cancer cell maintenance through suppression of apoptosis and tumor suppressor signaling. Furthermore, STAT5-mediated CD4+/CD25+ regulatory T cells (T<sub>regs</sub>) have been implicated in suppression of immunosurveillance. We discuss these roles for STAT3 and STAT5, and weigh the attractiveness of different modes of targeting each cancer therapy. Moreover, we discuss how anti-tumorigenic STATs, including STAT1 and STAT2, may be leveraged to suppress the pro-tumorigenic functions of STAT3/STAT5 signaling.https://www.mdpi.com/2072-6694/11/11/1716stat3stat5cancer progressioncancer-stem cellcytokinetherapy resistancemetastasisimmunosuppressiontumor microenvironmentproliferation |
| spellingShingle | Kelsey L. Polak Noah M. Chernosky Jacob M. Smigiel Ilaria Tamagno Mark W. Jackson Balancing STAT Activity as a Therapeutic Strategy Cancers stat3 stat5 cancer progression cancer-stem cell cytokine therapy resistance metastasis immunosuppression tumor microenvironment proliferation |
| title | Balancing STAT Activity as a Therapeutic Strategy |
| title_full | Balancing STAT Activity as a Therapeutic Strategy |
| title_fullStr | Balancing STAT Activity as a Therapeutic Strategy |
| title_full_unstemmed | Balancing STAT Activity as a Therapeutic Strategy |
| title_short | Balancing STAT Activity as a Therapeutic Strategy |
| title_sort | balancing stat activity as a therapeutic strategy |
| topic | stat3 stat5 cancer progression cancer-stem cell cytokine therapy resistance metastasis immunosuppression tumor microenvironment proliferation |
| url | https://www.mdpi.com/2072-6694/11/11/1716 |
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