STAT proteins: novel molecular targets for cancer drug discovery
Abstract
Signal Transducers and Activators of Transcription (STATs) are a family of cytoplasmic proteins with roles as signal messengers and transcription factors that participate in normal cellular responses to cytokines and growth factors. Frequently, however, abnormal activity of certain STAT family members, particularly Stat3 and Stat5, is associated with a wide variety of human malignancies, including hematologic, breast, head and neck, and prostate cancers. Application of molecular biology and pharmacology tools in disease-relevant models has confirmed Stat3 as having a causal role in oncogenesis, and provided validation of Stat3 as a target for cancer drug discovery and therapeutic intervention. Furthermore, a constitutively-active mutant form of Stat3 is sufficient to induce oncogenic transformation of cells, which form tumors in vivo. Constitutive activation of Stat3 signaling is accompanied by upregulation of cyclin D1, c-Myc, and Bcl-x, changes consistent with subversion of normal cellular growth and survival control mechanisms. Block of constitutive Stat3 signaling results in growth inhibition and apoptosis of Stat3-positive tumor cells in vitro and in vivo. The observed dependence of certain tumors on constitutive Stat3 signaling for growth and survival has wide implications for cancer therapy, offering the potential for preferential tumor cell killing. This review evaluates constitutive Stat3 activation as a 'cancer-causing' factor, and proposes a number of molecular str…
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A number of transformed cell lines as well as samples from human cancers are reported to contain constitutively activated STAT3.
“A number of transformed cell lines as well as samples from human cancers are reported to contain constitutively activated STAT3.”
From STAT3 Contributes to the Mitogenic Response of Hepatocytes during Liver Regeneration (2002) · cites this paper as [22]
Cites
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“…SHP-2, as well as a protein serine/threonine phosphatase, PP2A, are strongly implicated in STAT signaling, including Stat1, Stat3 and Stat5 (Ram and Waxman, 1997; Schaper et al., 1998; Shuai et al., 1996b; Stofega et al., 1998; Strehlow and Schindler, 1998; Woetmann et al., 1999; Yu et al., 2000).”
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- Authors
- Turkson, J., & Jove, R.
- Affiliations
- University of South Florida (US)
- ORCID
- Turkson, James
- Venue
- Oncogene
- Published
- 2000-12-27
- Volume
- 19
- Issue
- 56
- Pages
- 6613-6626
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W2056961869
- Cited by
- 643
- References
- 8
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 17 · 2023: 20 · 2022: 14 · 2021: 17 · 2020: 18 · 2019: 19 · 2018: 21 · 2017: 29 · 2016: 24 · 2015: 39 · 2014: 43 · 2013: 41 · 2012: 28
- FWCI
- 1.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cancer Mechanisms and Therapy
- Keywords
- STAT proteins, STAT3, STAT5, constitutive STAT3 activation, carcinogenesis, cancer drug targets, STAT3 inhibitor, apoptosis, cyclin D1, c-Myc, Bcl-x, tumor growth and survival, hematologic cancer, breast cancer, head and neck cancer, prostate cancer
- MeSH terms
- Antineoplastic Agents, DNA-Binding Proteins, Enzyme Inhibitors, Humans, Immunologic Deficiency Syndromes, Milk Proteins, Models, Biological, Neoplasms, Phosphoprotein Phosphatases, Receptors, Cell Surface, Drug Design, Signal Transduction, Trans-Activators, Drug Delivery Systems, Oligodeoxyribonucleotides, Antisense, Protein Kinase Inhibitors, STAT3 Transcription Factor, STAT5 Transcription Factor
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