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Janus kinase 1 plays a critical role in mammary cancer progression

ABSTRACT: Janus kinase 1 plays a critical role in mammary cancer progression

PROVIDER: PRJNA495488 | ENA |

REPOSITORIES: ENA

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Janus kinase 1 plays a critical role in mammary cancer progression

Project description:Janus kinases (JAKs) and their downstream STAT proteins play key roles in cytokine signaling, tissue homeostasis, and cancer development. Using a novel breast cancer model that conditionally lacks the Janus kinase 1, we show here that JAK1 is essential for IL-6 class inflammatory cytokine signaling and plays a critical role in metastatic cancer progression. JAK1 is indispensable for the oncogenic activation of STAT1, STAT3, and STAT6 in ERBB2-expressing cancer cells, suggesting that ERBB2 receptor tyrosine kinase complexes do not directly activate these STAT proteins in vivo. A genome-wide gene expression analysis revealed that JAK1 signaling has pleiotropic effects on several pathways associated with cancer progression. We established that FOS and MAP3K8 are targets of JAK1/STAT3 signaling that promote tumorsphere formation and cell migration. The results highlight the significance of JAK1 as a rational therapeutic target to block IL-6 class cytokines that are master regulators of cancer-associated inflammation.

2019-03-27 | GSE121064 | GEO

Janus Kinase 1 Plays a Critical Role in Mammary Cancer Progression.

Project description: Not available

| S-EPMC6431084 | biostudies-literature

Janus

Project description:Janus sp. overview

| PRJNA831994 | ENA

Chaperone-like protein DAY plays critical roles in photomorphogenesis

Project description:Chaperone-like protein DAY plays critical roles in photomorphogenesis

| PRJNA736856 | ENA

Janus piri

Project description:Janus piri Genome sequencing and assembly

| PRJNA784133 | ENA

Janus kinase 1 is essential for inflammatory cytokine signaling and mammary gland remodeling

Project description:Jak1 is a ubiquitously expressed tyrosine kinase that transduces extracellular signals from a variety of cytokines and their receptors to downstream signal transducers and activators of transcription (STATs). Since deficiency in Jak1 causes early neonatal lethality, we generated Jak1 conditional knockout mice to study the biological role of this kinase during the development of the mammary gland in adult females

2016-04-08 | GSE79452 | GEO

Effect of the janus kinase inhibitor ruxolitinib on gene expression of chronic lymphocytic leukemia cells in vivo

Project description:Symptomatic previously untreated chronic lymphocytic leukemia patients were treated with the janus kinase (JAK)-inhibitor ruxolitinib (clinicaltrials.gov, number NCT02015208). CLL cells from 6 of the patients were purified prior to commencing ruxolitinib and again 4 or 8 weeks after treatment and analyzed by RNAseq. Ruxolitinib induced a stereotyped response in all patients consisting of a rapid decrease in palpable lymphadenopathy accompanied by increased lymphocytosis and blood lactate dehydrogenase. This response was associated with evidence of inhibited JAK-signaling in CLL cells but activation of other oncogenic pathways.

2022-03-05 | GSE197811 | GEO

Epigenetic Gene Regulation by Janus Kinase 1 in Diffuse Large B Cell Lymphoma

Project description:Epigenetic Gene Regulation by Janus Kinase 1 in Diffuse Large B Cell Lymphoma

| PRJNA341330 | ENA

Janus kinase-Inhibition modulates hepatitis E virus infection

Project description:Background: Human hepatitis E virus (HEV) usually causes a self-limiting disease, but especially immunocompromised individuals are at risk to develop a chronic and severe course of infection. Janus kinase (JAK) inhibitors (JAKi) are a novel drug class for the treatment of autoimmune inflammatory rheumatic disease (AIRD). As JAKs play a key role in innate immunity, viral infections and reactivations are frequently reported during JAKi treatment in AIRD patients. The aim of this study was to characterize the influence of JAKis on HEV replication in vivo and in authentic cell culture models ex vivo. Methods: We evaluated liver enzymes of an AIRD patient under JAKi therapy with hepatitis E and HEV infections in a cohort of AIRD patients. Experiments with HEV were performed by infection of primary human hepatocytes (PHHs) followed by immunofluorescence staining of viral markers and transcriptomic analysis. Results: Acute hepatitis was observed in a patient with AIRD and concomitant HEV infection. No acute infection could be detected in the AIRD cohort. Infection experiments in PHHs displayed an up to 50-fold increase of progeny virus production during JAKi treatment and transcriptomic analysis revealed induction of antiviral programs during infection. This induction was perturbed in the presence of JAKis, concomitant with elevated HEV RNA levels. Conclusion: Therapeutic JAK inhibition increases HEV replication by modulating the HEV-triggered immune response. Therefore, clinical monitoring of HEV infection during JAKi treatment and in case of elevated liver enzymes should be considered.

2023-02-09 | GSE224795 | GEO

Non-oncogene addiction to SIRT3 plays a critical role in lymphomagenesis

Project description:Non-oncogene addiction to SIRT3 plays a critical role in lymphomagenesis

| PRJNA541280 | ENA