The role of JAK/STAT signaling pathway and its inhibitors in diseases

Xin, Ping; Xu, Xiaoyun; Deng, Chengjie; Liu, Shuang; Wang, Youzhi; Zhou, Xianwei; Ma, Hongxu; Donghua, Wei; Sun, Shiqin

doi:10.1016/j.intimp.2020.106210

Cited by 527 publications

(381 citation statements)

References 167 publications

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“…The nonreceptor tyrosine kinase associated with cytokine receptor so-called Janus kinase (JAK) phosphorylates the STAT. This pathway is called the JAK/STAT signaling pathway that is stimulated by cytokine [93]. Phosphorylated STAT1 forms a homodimer in the cytoplasm, and then it is transferred to the nucleus and binds to interferon γ-activated sequence (GAS) and stimulates the expression of interferon γ-induced genes.…”

Section: Helicobacter Outer Membrane Proteins and Gastric Cancermentioning

confidence: 99%

Molecular Mechanism of Helicobacter pylori-Induced Gastric Cancer

Alipour

2020

J Gastrointest Canc

150

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Introduction Various types of cancers threaten human life. The role of bacteria in causing cancer is controversial, but it has been determined that the Helicobacter pylori infection is one of the identified risk factors for gastric cancer. Helicobacter pylori infection is highly prevalent, and about half of the world , s population is infected with it. Objective The aim of this study was the role of Helicobacter pylori in the development of gastric cancer. Method We obtained information from previously published articles. Results and Conclusion The bacterium has various virulence factors, including cytotoxin-associated gene A, vacuolating cytotoxin A, and the different outer membrane proteins that cause cancer by different mechanisms. These virulence factors activate cell signaling pathways such as PI3-kinase/Akt, JAK/STAT and Ras, Raf, and ERK signaling that control cell proliferation. Uncontrolled proliferation can lead to cancer.

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Section: Helicobacter Outer Membrane Proteins and Gastric Cancermentioning

confidence: 99%

Molecular Mechanism of Helicobacter pylori-Induced Gastric Cancer

Alipour

2020

J Gastrointest Canc

150

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“…In recent years, the Janus kinase and signal transducer and activator of transcription (JAK-STAT) pathway has been shown to play a central role in both inflammatory and neurogenic pain processes associated with RA and other autoimmune disorders [20,21]. As such, blocking elements of JAK-STAT signaling represents an attractive therapeutic strategy [22][23][24].…”

Section: Introductionmentioning

confidence: 99%

Associations between Patient Global Assessment scores and pain, physical function, and fatigue in rheumatoid arthritis: a post hoc analysis of data from phase 3 trials of tofacitinib

Strand

Kaine²,

Alten

et al. 2020

Arthritis Res Ther

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Background Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We examined the degree to which Patient Global Assessment of Disease Activity (PtGA) was driven by patient-reported assessments of pain (Pain), physical function, and fatigue in patients receiving tofacitinib 5 mg twice daily or placebo, each with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Methods This post hoc analysis used data pooled from three randomized controlled trials in csDMARD-inadequate responder (csDMARD-IR) patients (ORAL Scan: NCT00847613; ORAL Standard: NCT00853385; ORAL Sync: NCT00856544). Using subgroup analysis from 2 × 2 tables, associations between PtGA and Pain, Health Assessment Questionnaire-Disability Index (HAQ-DI), and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) at month 3 were evaluated using Pearson’s Phi correlation coefficients. To support the main analysis, associations between select patient-reported outcomes (PROs) were also evaluated in csDMARD-naïve (ORAL Start; NCT01039688) and biologic (b)DMARD-IR (ORAL Step; NCT00960440) patients. Results Across csDMARD-IR treatment groups, low disease activity (defined as PtGA ≤ 20 mm), and moderate (≥ 30%) and substantial (≥ 50%) improvements from baseline in PtGA were associated with mild Pain (Visual Analog Scale score ≤ 20 mm), and moderate (≥ 30%) and substantial (≥ 50%) improvements from baseline in Pain; lack of Pain improvement was associated with little/no improvement in PtGA. In contrast, large proportions of csDMARD-IR patients who reported PtGA improvements did not report HAQ-DI or FACIT-F scores ≥ normative values (≤ 0.25 and ≥ 43.5, respectively) or changes in HAQ-DI or FACIT-F scores ≥ minimum clinically important difference (≥ 0.22 and ≥ 4.0, respectively). Generally, PtGA and Pain outcomes were moderately-to-strongly correlated at month 3 in csDMARD-IR patients, with weaker correlations evident between PtGA and HAQ-DI/FACIT-F outcomes. Similar findings were generally evident in csDMARD-naïve and bDMARD-IR patients. Conclusions This analysis supports the role of Pain as a key driver of PtGA in RA; physical function and fatigue play lesser roles in patients’ perceptions of disease activity. These findings corroborate the importance of improved PROs and attainment of low symptom states for optimizing patient care. Trial registration Clinicaltrials.gov: NCT00847613 (registered: February 19, 2009); NCT00853385 (registered: March 2, 2009); NCT00856544 (registered: March 5, 2009); NCT01039688 (registered: December 25, 2009); NCT00960440 (registered: August 17, 2009)

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“…In light of the tremendous importance of cytokines in health and disease, recent efforts have focused on harnessing structural and functional data interrogating cytokine-receptor interactions and functionality toward the development of potent antagonists and agonists that can modulate cytokine-mediated signaling ( 115 ) ( Figure 3 ). Such modulators would be expected to have distinct modes of action compared to already available inhibitors known to target intracellular portions of cytokine receptors or specific intracellular signaling components downstream of cytokine-dependent receptor activation ( 116 , 117 ). Nevertheless, extracellular portions of cytokine receptors and the activating cytokines are attractive targets in their own right.…”

Section: Strategies To Modulate Signaling Mediated By Tslp and Il-7mentioning

confidence: 99%

Modulation of Signaling Mediated by TSLP and IL-7 in Inflammation, Autoimmune Diseases, and Cancer

Marković

Savvides

2020

Front. Immunol.

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Thymic Stromal Lymphopoietin (TSLP) and Interleukin-7 (IL-7) are widely studied cytokines within distinct branches of immunology. On one hand, TSLP is crucially important for mediating type 2 immunity at barrier surfaces and has been linked to widespread allergic and inflammatory diseases of the airways, skin, and gut. On the other hand, IL-7 operates at the foundations of T-cell and innate lymphoid cell (ILC) development and homeostasis and has been associated with cancer. Yet, TSLP and IL-7 are united by key commonalities in their structure and the structural basis of the receptor assemblies they mediate to initiate cellular signaling, in particular their cross-utilization of IL-7Rα. As therapeutic targeting of TSLP and IL-7 via diverse approaches is reaching advanced stages and in light of the plethora of mechanistic and structural data on receptor signaling mediated by the two cytokines, the time is ripe to provide integrated views of such knowledge. Here, we first discuss the major pathophysiological roles of TSLP and IL-7 in autoimmune diseases, inflammation and cancer. Subsequently, we curate structural and mechanistic knowledge about receptor assemblies mediated by the two cytokines. Finally, we review therapeutic avenues targeting TSLP and IL-7 signaling. We envision that such integrated view of the mechanism, structure, and modulation of signaling assemblies mediated by TSLP and IL-7 will enhance and fine-tune the development of more effective and selective approaches to further interrogate the role of TSLP and IL-7 in physiology and disease.

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The role of JAK/STAT signaling pathway and its inhibitors in diseases

Cited by 527 publications

References 167 publications

Molecular Mechanism of Helicobacter pylori-Induced Gastric Cancer

Molecular Mechanism of Helicobacter pylori-Induced Gastric Cancer

Associations between Patient Global Assessment scores and pain, physical function, and fatigue in rheumatoid arthritis: a post hoc analysis of data from phase 3 trials of tofacitinib

Modulation of Signaling Mediated by TSLP and IL-7 in Inflammation, Autoimmune Diseases, and Cancer

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