Drosophila Jak/STAT Signaling: Regulation and Relevance in Human Cancer and Metastasis

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...

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Autores principales: Trivedi, Sunny, Starz-Gaiano, Michelle
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320922/
https://www.ncbi.nlm.nih.gov/pubmed/30558204
http://dx.doi.org/10.3390/ijms19124056
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author Trivedi, Sunny
Starz-Gaiano, Michelle
author_facet Trivedi, Sunny
Starz-Gaiano, Michelle
author_sort Trivedi, Sunny
collection PubMed
description 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.
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spelling pubmed-63209222019-01-07 Drosophila Jak/STAT Signaling: Regulation and Relevance in Human Cancer and Metastasis Trivedi, Sunny Starz-Gaiano, Michelle Int J Mol Sci Review 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. MDPI 2018-12-14 /pmc/articles/PMC6320922/ /pubmed/30558204 http://dx.doi.org/10.3390/ijms19124056 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Trivedi, Sunny
Starz-Gaiano, Michelle
Drosophila Jak/STAT Signaling: Regulation and Relevance in Human Cancer and Metastasis
title Drosophila Jak/STAT Signaling: Regulation and Relevance in Human Cancer and Metastasis
title_full Drosophila Jak/STAT Signaling: Regulation and Relevance in Human Cancer and Metastasis
title_fullStr Drosophila Jak/STAT Signaling: Regulation and Relevance in Human Cancer and Metastasis
title_full_unstemmed Drosophila Jak/STAT Signaling: Regulation and Relevance in Human Cancer and Metastasis
title_short Drosophila Jak/STAT Signaling: Regulation and Relevance in Human Cancer and Metastasis
title_sort drosophila jak/stat signaling: regulation and relevance in human cancer and metastasis
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320922/
https://www.ncbi.nlm.nih.gov/pubmed/30558204
http://dx.doi.org/10.3390/ijms19124056
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