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STAT3 Target Genes Relevant to Human Cancers

Richard L. Carpenter, +1 more
- 16 Apr 2014 - 
- Vol. 6, Iss: 2, pp 897-925
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TLDR
A review will be primarily focused on STAT3 downstream target genes that have been validated to associate with tumorigenesis and/or malignant biology of human cancers.
Abstract
Since its discovery, the STAT3 transcription factor has been extensively studied for its function as a transcriptional regulator and its role as a mediator of development, normal physiology, and pathology of many diseases, including cancers. These efforts have uncovered an array of genes that can be positively and negatively regulated by STAT3, alone and in cooperation with other transcription factors. Through regulating gene expression, STAT3 has been demonstrated to play a pivotal role in many cellular processes including oncogenesis, tumor growth and progression, and stemness. Interestingly, recent studies suggest that STAT3 may behave as a tumor suppressor by activating expression of genes known to inhibit tumorigenesis. Additional evidence suggested that STAT3 may elicit opposing effects depending on cellular context and tumor types. These mixed results signify the need for a deeper understanding of STAT3, including its upstream regulators, parallel transcription co-regulators, and downstream target genes. To help facilitate fulfilling this unmet need, this review will be primarily focused on STAT3 downstream target genes that have been validated to associate with tumorigenesis and/or malignant biology of human cancers.

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Constitutive activation of STAT3 in breast cancer cells: A review.

TL;DR: This review provides a full spectrum of STAT3's involvement in breast cancers by consolidating the knowledge about its role in breast cancer development at multiple levels: its differential regulation by different receptor signaling pathways, its downstream target genes, and modification of its transcriptional activity by its coregulatory transcription factors.
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Th17-type cytokines, IL-6 and TNF-α synergistically activate STAT3 and NF-kB to promote colorectal cancer cell growth.

TL;DR: The data suggest that strategies aimed at the cotargeting of STAT3/NF-kB activation and interaction between them might represent an attractive and novel approach to combat CRC.
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Interleukin-6: designing specific therapeutics for a complex cytokine

TL;DR: The roles of IL-6 in health and disease are overviewed and progress with several approaches of inhibitingIL-6-signalling is analyzed, with the aim of illuminating when and how to apply IL- 6 blockade.
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A Potent and Selective Small-Molecule Degrader of STAT3 Achieves Complete Tumor Regression In Vivo

TL;DR: SD-36 achieves complete and long-lasting tumor regression in multiple xenograft mouse models at well-tolerated dose schedules and is a promising cancer therapeutic strategy.
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LSD1/KDM1A inhibitors in clinical trials: advances and prospects.

TL;DR: This review is to provide a comprehensive overview of LSD1 inhibitors in clinical trials including molecular mechanistic studies, clinical efficacy, adverse drug reactions, and PD/PK studies and offer prospects in this field.
References
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Journal ArticleDOI

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Journal ArticleDOI

Stat3 as an Oncogene

TL;DR: Substitution of two cysteine residues within the C-terminal loop of the SH2 domain of Stat3 produces a molecule that dimerizes spontaneously, binds to DNA, and activates transcription.
Journal ArticleDOI

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