Janus Kinase/Signal Converters, and the Transcriptional Activator Signaling Pathway Promotes Lung Cancer Through Increasing M2 Macrophage

2021 ◽  
Vol 11 (4) ◽  
pp. 605-611
Author(s):  
Xinliang Zhan ◽  
Yan Wang ◽  
Jing Yang
Keyword(s):  
Lung Cancer ◽  
Bone Marrow ◽  
Signaling Pathway ◽  
Cancer Progression ◽  
Primary Lung Cancer ◽  
Janus Kinase ◽  
M2 Macrophage ◽  
Migration Ability ◽  
Stat Signaling ◽  
The Impact

Accumulating evidence highlights the salient function of JAK/STAT signaling pathway in tumorigenesis and development. But the mechanism of JAK/STAT signaling in lung cancer remains elusive. This study assessed the impact of JAK/STAT on lung tumorigenesis and its interaction with microenvironment. Mouse model of primary lung cancer was established and then treated with JAK/STAT inhibitor. Immunofluorescence was performed to analyze fluorescent labels. Transwell assay determined the cell migration ability, and Western blot, immunohistochemistry, and immunofluorescence to detect the expression of JAK/STAT key proteins. Cell proliferation was measured by Kit-8 and colony formation. JAK/STAT key proteins were upregulated in lung cancer models. Inhibition of JAK/STAT led to a decrease in proliferative, migratory and invasive capability of lung cancer cells and macrophages from bone marrow and spleen. The cell invasion ability in the bone marrow and the proliferation of macrophages in the treatment group was weakened. When co-cultured with the treated macrophages, the proliferation of LLC1 cells was inhibited. Furthermore, in vitro flow cytometry indicated that JAK/STAT affected lung cancer progression by affecting the polarization of M1/M2 macrophages. Taken altogether, JAK/STAT signal enhances M2 macrophage expression and promotes lung cancer progression.

scholarly journals The impact of enhanced recovery after surgery (ERAS) protocol compliance on morbidity from resection for primary lung cancer

2018 ◽  
Vol 155 (4) ◽  
pp. 1843-1852 ◽  
Author(s):  
Luke J. Rogers ◽  
David Bleetman ◽  
David E. Messenger ◽  
Natasha A. Joshi ◽  
Lesley Wood ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Enhanced Recovery ◽  
Enhanced Recovery After Surgery ◽  
Primary Lung Cancer ◽  
Protocol Compliance ◽  
Eras Protocol ◽  
The Impact

Constitutive activation of STAT-3 and downregulation of SOCS-3 expression induced by adrenalectomy

2001 ◽  
Vol 281 (6) ◽  
pp. R2048-R2058 ◽  
Author(s):  
Abram M. Madiehe ◽  
Ling Lin ◽  
Christy White ◽  
H. Doug Braymer ◽  
George A. Bray ◽  
...  
Keyword(s):  
Dna Binding ◽  
Signaling Pathway ◽  
Leptin Receptor ◽  
Binding Activity ◽  
Janus Kinase ◽  
Adrenal Steroids ◽  
Western Blots ◽  
Protein Levels ◽  
Dna Binding Activity ◽  
Stat Signaling

Removal of adrenal steroids by adrenalectomy (ADX) slows or reverses the development of many forms of obesity in rodents, including those that are leptin or leptin receptor deficient. Obesity is associated with hyperleptinemia and leptin resistance. We hypothesized that glucocorticoids impair leptin receptor signaling and that removal thereof would activate the Janus kinase (JAK)-signal transducers and activators of transcription (STAT) signaling pathway. The inhibitory effect of leptin (2.5 μg icv) on food intake was enhanced in ADX rats. A combination of ribonuclease protection assays, RT-PCR, Western blots, and mobility shift assays was used to evaluate the leptin signaling pathway in whole hypothalami from sham-operated, ADX and corticosterone-replaced ADX (ADX-R) Sprague-Dawley rats that were treated acutely with either saline vehicle or leptin intracerebroventricularly. ADX increased the expression of leptin receptor mRNA, increased STAT-3 mRNA and protein levels, induced constitutive STAT-3 phosphorylation and DNA binding activity, and also reduced suppressor of cytokine signaling-3 (SOCS-3) mRNA and protein levels. ADX and leptin treatment increased STAT-3 phosphorylation, but with no concomitant increase in DNA binding activity. Leptin and ADX decreased NPY mRNA expression, but their combination did not further decrease NPY mRNA. Corticosterone supplementation of ADX rats partially reversed many of these effects. In conclusion, ADX through activation of STAT-3 and inhibition of SOCS-3 activates the JAK-STAT signaling pathway. These effects most probably explain the ability to prevent the development of obesity by removal of adrenal steroids.

scholarly journals Systemic Platelet-activating Factor Receptor Activation Augments Experimental Lung Tumor Growth and Metastasis

2014 ◽  
Vol 7 ◽  
pp. CGM.S14501 ◽  
Author(s):  
Patrick C. Hackler ◽  
Sarah Reuss ◽  
Raymond L. Konger ◽  
Jeffrey B. Travers ◽  
Ravi P. Sahu
Keyword(s):  
Lung Cancer ◽  
Tumor Growth ◽  
Cancer Progression ◽  
Lung Tumor ◽  
Platelet Activating Factor ◽  
Receptor Activation ◽  
Dependent Manner ◽  
Melanoma Tumor ◽  
Tumor Growth And Metastasis ◽  
The Impact

Pro-oxidative stressors including cigarette smoke (CS) generate novel lipids with platelet-activated factor-receptor (PAF-R) agonistic activity mediate systemic immunosuppression, one of the most recognized events in promoting carcinogenesis. Our previous studies have established that these oxidized-PAF-R-agonists augment murine B16F10 melanoma tumor growth in a PAF-R-dependent manner because of its effects on host immunity. As CS generates PAF-R agonists, the current studies sought to determine the impact of PAF-R agonists on lung cancer growth and metastasis. Using the murine Lewis Lung Carcinoma (LLC1) model, we demonstrate that treatment of C57BL/6 mice with a PAF-R agonist augments tumor growth and lung metastasis in a PAF-R-dependent manner as these findings were not seen in PAF-R-deficient mice. Importantly, this effect was because of host rather than tumor cells PAF-R dependent as LLC1 cells do not express functional PAF-R. These findings indicate that experimental lung cancer progression can be modulated by the PAF system.

scholarly journals The Descriptive Epidemiology of Primary Lung Cancer in an Alberta Cohort with a Mutivariate Analysis of Survival to Two Years

2003 ◽  
Vol 10 (8) ◽  
pp. 435-441 ◽  
Author(s):  
Sandor J Demeter ◽  
Chester Chmielowiec ◽  
Wayne Logus ◽  
Pauline Benkovska-Angelova ◽  
Philip Jacobs ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
American Literature ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Primary Lung Cancer ◽  
Case Fatality ◽  
Nonsmall Cell Lung Cancer ◽  
Small Cell ◽  
The Impact

BACKGROUND: Lung cancer contributes significantly to cancer morbidity and mortality. Although case fatality rates have not changed significantly over the past few decades, there have been advances in the diagnosis, staging and management of lung cancer.OBJECTIVE: To describe the epidemiology of primary lung cancer in an Alberta cohort with an analysis of factors contributing to survival to two years.PATIENTS AND METHODS: Six hundred eleven Albertans diagnosed with primary lung cancer in 1998 were identified through the Alberta Cancer Registry. Through a chart review, demographic and clinical data were collected for a period of up to two years from the date of diagnosis.RESULTS: The mean age at diagnosis was 66.5 years. The majority of cases (92%) were smokers. Adenocarcinoma, followed by squamous cell carcinoma, were the most frequent nonsmall cell lung cancer histologies. Adenocarcinoma was more frequent in women, and squamous cell carcinoma was more frequent in men. The overall two- year survival rates for nonsmall cell, small cell and other lung cancers were 24%, 10% and 13%, respectively. In multivariate analysis, stage, thoracic surgery and chemotherapy were significantly associated with survival to two years in nonsmall cell carcinoma; only stage and chemotherapy were significant in small cell carcinoma.CONCLUSIONS: This study provides a Canadian epidemiological perspective, which generally concurs with the North American literature. Continued monitoring of the epidemiology of lung cancer is essential to evaluate the impact of advances in the diagnosis, staging and management of lung cancer. Further clinical and economic analysis, based on data collected on this cohort, is planned.

Signal Transducer and Activator of Transcription6 Signaling Pathway in Tumor-Associated Macrophage Aggravates Lung Cancer Progression

2021 ◽  
Vol 11 (9) ◽  
pp. 1707-1713
Author(s):  
Jun Wan ◽  
Jian Wang ◽  
Qiurong Huang ◽  
Guanggui Ding ◽  
Xiean Ling
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
T Cell ◽  
Cancer Progression ◽  
Cancer Tissue ◽  
M2 Macrophage ◽  
Normal Tissues ◽  
Tumor Associated Macrophage ◽  
M1 Macrophage ◽  
And Migration

Lung cancer is a most common cancer worldwide. Tumor-associated macrophage (TAM) is known a key effector cell in tumor microenvironment. Meanwhile, STAT6 is crucial to cancer development. We aimed to determine the interaction between STAT6 and TAMs in lung cancer. In this work, firstly, we established mouse model of lung cancer. Then, immunofluorescence was performed to determine STAT6 and CD206 level in lung cancer tissue and adjacent normal tissues as well as model mice. RT-qPCR was applied to detect differentiation of macrophage and determine related gene expression. After treatment of siRNA of STAT6 or STAT6 inhibitor (AS1517499), Transwell assay and MTT were used to determine cell proliferation and migration. STAT6 was upregulated in lung cancer tissues while arginase was more active in M2 macrophage rather than M1 macrophage. Transfection of si-STAT6 not only decreased differentiation in M2 macrophage but also inhibited proliferative, migratory and invasive ability of cancer cells while AS1517499 led to reduced tumor growth. STAT6 inhibition caused decreased expression of M2 macrophages. Similarly, intratumoral T cell markers showed that CD8+T cell gene expression and CD4-mediated T cell marker FoxP3 was increased slightly. Taken altogether, macrophage-STAT6 promotes cell migration and proliferation in lung cancer.

scholarly journals Structural insights and evaluation of the potential impact of missense variants on the interactions of SLIT2 with ROBO1/4 in cancer progression

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Debmalya Sengupta ◽  
Gairika Bhattacharya ◽  
Sayak Ganguli ◽  
Mainak Sengupta
Keyword(s):  
Lung Cancer ◽  
Cancer Progression ◽  
Structural Parameters ◽  
Homology Modelling ◽  
Missense Variants ◽  
Potential Impact ◽  
The Impact ◽  
Structural Insights ◽  
Rigid Docking

AbstractThe cognate interaction of ROBO1/4 with its ligand SLIT2 is known to be involved in lung cancer progression. However, the precise role of genetic variants, disrupting the molecular interactions is less understood. All cancer-associated missense variants of ROBO1/4 and SLIT2 from COSMIC were screened for their pathogenicity. Homology modelling was done in Modeller 9.17, followed by molecular simulation in GROMACS. Rigid docking was performed for the cognate partners in PatchDock with refinement in HADDOCK server. Post-docking alterations in conformational, stoichiometric, as well as structural parameters, were assessed. The disruptive variants were ranked using a weighted scoring scheme. In silico prioritisation of 825 variants revealed 379 to be potentially pathogenic out of which, about 12% of the variants, i.e. ROBO1 (14), ROBO4 (8), and SLIT2 (23) altered the cognate docking. Six variants of ROBO1 and 5 variants of ROBO4 were identified as "high disruptors" of interactions with SLIT2 wild type. Likewise, 17 and 13 variants of SLIT2 were found to be "high disruptors" of its interaction with ROBO1 and ROBO4, respectively. Our study is the first report on the impact of cancer-associated missense variants on ROBO1/4 and SLIT2 interactions that might be the drivers of lung cancer progression.

Atomistic insight into the inhibition mechanisms of suppressors of cytokine signaling on Janus kinase

2019 ◽  
Vol 21 (24) ◽  
pp. 12905-12915 ◽  
Author(s):  
Yaru Wei ◽  
Zhiyang Zhang ◽  
Nai She ◽  
Xin Chen ◽  
Yuan Zhao ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Negative Feedback ◽  
Janus Kinase ◽  
Cytokine Signaling ◽  
Signal Transducer ◽  
Jak Kinase ◽  
Stat Signaling ◽  
Suppressors Of Cytokine Signaling ◽  
Insight Into

Suppressors of cytokine signaling (SOCS) act as negative feedback regulators of the Janus kinase/signal transducer (JAK–STAT) signaling pathway by inhibiting the activity of JAK kinase.

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