Drosophila Jak/STAT Signaling: Regulation and Relevance in Human Cancer and Metastasis
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Author/Creator ORCID
Date
2018-12-14
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Citation of Original Publication
Sunny Trivedi and Michelle Starz-Gaiano, Drosophila Jak/STAT Signaling: Regulation and Relevance in Human Cancer and Metastasis, Int. J. Mol. Sci. 2018, 19(12), 4056; https://doi.org/10.3390/ijms19124056
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Attribution 4.0 International (CC BY 4.0)
Attribution 4.0 International (CC BY 4.0)
Abstract
Over the past three-decades, Janus kinase (Jak) and signal transducer and activator
of transcription (STAT) signaling has emerged as a paradigm to understand the involvement of
signal transduction in development and disease pathology. At the molecular level, cytokines and
interleukins steer Jak/STAT signaling to transcriptional regulation of target genes, which are involved
in cell differentiation, migration, and proliferation. Jak/STAT signaling is involved in various types
of blood cell disorders and cancers in humans, and its activation is associated with carcinomas that
are more invasive or likely to become metastatic. Despite immense information regarding Jak/STAT
regulation, the signaling network has numerous missing links, which is slowing the progress towards
developing drug therapies. In mammals, many components act in this cascade, with substantial
cross-talk with other signaling pathways. In Drosophila, there are fewer pathway components,
which has enabled significant discoveries regarding well-conserved regulatory mechanisms. Work
across species illustrates the relevance of these regulators in humans. In this review, we showcase
fundamental Jak/STAT regulation mechanisms in blood cells, stem cells, and cell motility. We examine
the functional relevance of key conserved regulators from Drosophila to human cancer stem cells and
metastasis. Finally, we spotlight less characterized regulators of Drosophila Jak/STAT signaling, which
stand as promising candidates to be investigated in cancer biology. These comparisons illustrate the
value of using Drosophila as a model for uncovering the roles of Jak/STAT signaling and the molecular
means by which the pathway is controlled.