STAT3 and metabolism: How many ways to use a single molecule?

Demaria, Marco; Camporeale, Annalisa; Poli, Valeria

doi:10.1002/ijc.28767

Cited by 56 publications

(49 citation statements)

References 68 publications

(114 reference statements)

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“…For example, several roles were identified for STAT proteins that are independent of CytoRs and JAKs. These include the control of cell growth, differentiation, chemotaxis and immune responses in slime mold downstream of G-protein-coupled receptors (29), and the regulation of metabolic functions in vertebrates by unphosphorylated STATs (40,41). Similarly, several SOCS members are principally involved in the regulation of growth factor receptors and other pathways (39).…”

Section: Emergence Of the Pathwaymentioning

confidence: 99%

Evolution of Cytokine Receptor Signaling

Liongue

Sertori

Ward

2016

The Journal of Immunology

103

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Cytokines represent essential mediators of cell–cell communication with particularly important roles within the immune system. These secreted factors are produced in response to developmental and/or environmental cues and act via cognate cytokine receptors on target cells, stimulating specific intracellular signaling pathways to facilitate appropriate cellular responses. This review describes the evolution of cytokine receptor signaling, focusing on the class I and class II receptor families and the downstream JAK–STAT pathway along with its key negative regulators. Individual components generated over a long evolutionary time frame coalesced to form an archetypal signaling pathway in bilateria that was expanded extensively during early vertebrate evolution to establish a substantial “core” signaling network, which has subsequently undergone limited diversification within discrete lineages. The evolution of cytokine receptor signaling parallels that of the immune system, particularly the emergence of adaptive immunity, which has likely been a major evolutionary driver.

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Section: Emergence Of the Pathwaymentioning

confidence: 99%

Evolution of Cytokine Receptor Signaling

Liongue

Sertori

Ward

2016

The Journal of Immunology

103

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“…Importantly, the growth and glucose uptake of developing mammary tumors was severely compromised in mice treated with the STAT3 inhibitor S3I-201, 83 which negated HIF-1α expression and its induction of the noncanonical STAT3 activator, pyruvate kinase M2 84 , 85 . Additionally, STAT3 enhances carcinoma cell survival during metastasis by inhibiting the expression of components of the electron transport chain, thereby decreasing mitochondrial respiration and the production of reactive oxygen species 85 . Taken together, these findings highlight novel nongenomic STAT3 activities that figure prominently in driving carcinoma development and metastatic progression.…”

Section: Nongenomic Stat3 Signalingmentioning

confidence: 99%

STAT3 and epithelial–mesenchymal transitions in carcinomas

et al. 2014

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Cellular programs coupled to cycles of epithelial–mesenchymal transitions (EMTs) play critical roles during embryogenesis, as well as during tissue development, remodeling, and repair. Research over the last decade has established the importance of an ever-expanding list of master EMT transcription factors, whose activity is regulated by STAT3 and function to stimulate the rapid transition of cells between epithelial and mesenchymal phenotypes. Importantly, inappropriate reactivation of embryonic EMT programs in carcinoma cells underlies their metastasis to distant organ sites, as well as their acquisition of stem cell-like and chemoresistant phenotypes operant in eliciting disease recurrence. Thus, targeted inactivation of master EMT transcription factors may offer new inroads to alleviate metastatic disease. Here we review the molecular, cellular, and microenvironmental factors that contribute to the pathophysiological activities of STAT3 during its regulation of EMT programs in human carcinomas.

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“…Several recent studies have reported the nontranscriptional role of STAT3 in cellular metabolic processes. 34–36 We believe that the functional motifs uniquely found in DMXL2 isoform 3 are involved in the biological processes predicted with high fold changes for this protein.…”

Section: Discussionmentioning

confidence: 94%

Computational Inferences of the Functions of Alternative/Noncanonical Splice Isoforms Specific to HER2+/ER–/PR– Breast Cancers, a Chromosome 17 C-HPP Study

et al. 2015

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This study was conducted as a part of the Chromosome-Centric Human Proteome Project (C-HPP) of the Human Proteome Organization. The main objective is to identify and evaluate functionality of a set of specific noncanonical isoforms expressed in HER2-neu positive, estrogen receptor negative (ER−), and progesterone receptor negative (PR−) breast cancers (HER2+/ER−/PR− BC), an aggressive subtype of breast cancers that cause significant morbidity and mortality. We identified 11 alternative splice isoforms that were differentially expressed in HER2+/ER−/PR− BC compared to normal mammary, triple negative breast cancer and triple positive breast cancer tissues (HER2+/ER+/PR+). We used a stringent criterion that differentially expressed noncanonical isoforms (adjusted p value < 0.05) and have to be expressed in all replicates of HER2+/ER−/PR− BC samples, and the trend in differential expression (up or down) is the same in all comparisons. Of the 11 protein isoforms, six were overexpressed in HER2+/ER−/PR− BC. We explored possible functional roles of these six proteins using several complementary computational tools. Biological processes including cell cycle events and glycolysis were linked to four of these proteins. For example, glycolysis was the top ranking functional process for DMXL2 isoform 3, with a fold change of 27 compared to just two for the canonical protein. No previous reports link DMXL2 with any metabolic processes; the canonical protein is known to participate in signaling pathways. Our results clearly indicate distinct functions for the six overexpressed alternative splice isoforms, and these functions could be specific to HER2+/ER−/PR− tumor progression. Further detailed analysis is warranted as these proteins could be explored as potential biomarkers and therapeutic targets for HER2+/ER−/PR− BC patients.

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STAT3 and metabolism: How many ways to use a single molecule?

Cited by 56 publications

References 68 publications

Evolution of Cytokine Receptor Signaling

Evolution of Cytokine Receptor Signaling

STAT3 and epithelial–mesenchymal transitions in carcinomas

Computational Inferences of the Functions of Alternative/Noncanonical Splice Isoforms Specific to HER2+/ER–/PR– Breast Cancers, a Chromosome 17 C-HPP Study

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