IL-13 receptor α2 is a negative prognostic factor in human lung cancer and stimulates lung cancer growth in mice

Wu, Xiao; Zhang, Jin Jun; He, Chao

doi:10.18632/oncotarget.5361

Cited by 30 publications

(22 citation statements)

References 28 publications

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“…Our team has discovered that IRS-1 activated the PI3K-Akt signaling pathway to enhance the proliferation of the primary rat osteoblasts (Ma et al, 2015). Although we found that the increased TAZ expression induced by IGF1 is mostly mediated by the MEK-ERK pathway rather than the PI3K-Akt signaling pathway in our previous research (Xue et al, 2013), Xie et al (2015) reported that inhibition of the PI3K-Akt pathway could attenuate the activation of TAZ expression in lung cancer cells. Our results revealed that the PI3K-Akt pathway inhibitor, LY294002, offsets the IRS-1 induced upregulation of TAZ expression, which points to a link between the IRS-1/PI3K-Akt signaling pathway and the TAZ/RUNX2 transcriptional complex during osteoblast maturation.…”

Section: Discussioncontrasting

confidence: 66%

IRS-1 increases TAZ expression and promotes osteogenic differentiation in rat bone marrow mesenchymal stem cells

Wang

Xue

et al. 2018

Biology Open

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Whether insulin receptor substrate 1 (IRS-1) inhibits or promotes the osteogenic proliferation and differentiation in vitro remains controversial. Transcriptional co-activator with PDZ-binding motif (TAZ) plays a vital role in the osteogenesis of bone marrow mesenchymal stem cells (BMSCs), and strongly activates the expression of the osteogenic differentiation markers. In this study, we found that IRS-1 and TAZ followed similar increasing expression patterns at the early stage of osteogenic differentiation. Knocking down IRS-1 decreased the TAZ, RUNX2 and OCN expression, and overexpressing IRS induced the upregulation of the TAZ, RUNX2 and OCN expression. Furthermore, our results showed that it was LY294002 (the PI3K-Akt inhibitor), other than UO126 (the MEK-ERK inhibitor), that inhibited the IRS-1 induced upregulation of TAZ expression. Additionally, SiTAZ blocked the cell proliferation in G1 during the osteogenic differentiation of BMSCs. Taken together, we provided evidence to demonstrate that IRS-1 gene modification facilitates the osteogenic differentiation of rat BMSCs by increasing TAZ expression through the PI3K-Akt signaling pathway..

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Section: Discussioncontrasting

confidence: 66%

IRS-1 increases TAZ expression and promotes osteogenic differentiation in rat bone marrow mesenchymal stem cells

Wang

Xue

et al. 2018

Biology Open

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“…With respect to IL-13, a recent study observed the highest expression level of IL-13 in LC in the SQC subtype, followed by the ADC subtype [139]. Moreover, a clear association between IL-13 receptor subunit alpha-2 overexpression and poor survival in resected NSCLC patients has been shown [140]. There are other profibrotic cytokines besides IL-13 that are also associated with IPF.…”

Section: Principal Fibrogenic Molecules and Signal Transduction Pamentioning

confidence: 99%

“…In LC, the CCL2/CCR2 (chemokine receptor type 2) axis is also important in several aspects of tumorigenesis. One of its most important roles is the generation of new vascular structures that allow tumour growth [140]. However, there is evidence of an association between CCL2 in cancer cells and better survival in NSCLC patients [143].…”

Section: Principal Fibrogenic Molecules and Signal Transduction Pamentioning

confidence: 99%

Idiopathic Pulmonary Fibrosis and Lung Cancer: Mechanisms and Molecular Targets

Ballester

Milara

Cortijo

2019

IJMS

241

175

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Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial pulmonary disease with a median survival of 2–4 years after diagnosis. A significant number of IPF patients have risk factors, such as a history of smoking or concomitant emphysema, both of which can predispose the patient to lung cancer (LC) (mostly non-small cell lung cancer (NSCLC)). In fact, IPF itself increases the risk of LC development by 7% to 20%. In this regard, there are multiple common genetic, molecular, and cellular processes that connect lung fibrosis with LC, such as myofibroblast/mesenchymal transition, myofibroblast activation and uncontrolled proliferation, endoplasmic reticulum stress, alterations of growth factors expression, oxidative stress, and large genetic and epigenetic variations that can predispose the patient to develop IPF and LC. The current approved IPF therapies, pirfenidone and nintedanib, are also active in LC. In fact, nintedanib is approved as a second line treatment in NSCLC, and pirfenidone has shown anti-neoplastic effects in preclinical studies. In this review, we focus on the current knowledge on the mechanisms implicated in the development of LC in patients with IPF as well as in current IPF and LC-IPF candidate therapies based on novel molecular advances.

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“…Studies showed that IL13Rα2 positively regulates HCC through activation of the TGF-β1 promoter, increasing TGF-β1 production and fibrosis progression [11,15]. Others suggested that it might mediate its effect via activating the Yes-associated protein (YAP) and/or transcriptional coactivator with PDZ-binding motif (TAZ) in hippo signaling [15,16]. Interestingly, the hippo pathway transcriptional activator TAZ was recently correlated in fibrosis progression in NASH [17].…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms in Interleukin 13 Signaling and Interacting Genes Predict Advanced Fibrosis and Hepatocellular Carcinoma Development in Non-Alcoholic Steatohepatitis

El-Derany

2020

Biology

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Background: non-alcoholic steatohepatitis (NASH) recently headlined hepatocellular carcinoma (HCC) worldwide. This study aims to unveil the role of some unaddressed critical players that might aid in understanding, predicting, and targeting NASH and NASH-HCC. Methods: Serum interleukin 13 (IL-13) levels and single nucleotide polymorphisms (SNPs) within interleukin (IL)-13 rs20541, IL-13 receptors (IL-13R1) rs2248841, (IL-13R2) rs5946040, signal transducer activator of transcription 6 (STAT6) rs167769, yes-associated protein (YAP1) rs11225163, programmed death-ligand 1 (PD-L1) rs2282055, and programmed death-ligand 2 (PD-L2) rs7854413 genes were analyzed by qRT-PCR. Multiple stepwise regression analysis was performed on a cohort of 134 Egyptian male patients diagnosed with NASH and NASH-HCC. RESULTS: higher serum alpha-fetoprotein (AFP) and higher serum IL-13 levels were directly associated with HCC development in NASH (odds ratio (OR) 19.6 and 1.9 p < 0.01). Reversibly, the presence of the C/C genotype in STAT6 rs167769 and the C allele carrier YAP1 rs11225163 were inversely associated with HCC in NASH patients (OR 0.015 and 0.047 p < 0.01). A predictive model was formulated with 97.5% specificity, 90.9% sensitivity, and 94.8% accuracy. Moreover, higher serum IL-13 levels and the presence of PD-L2 rs7854413 C allele carriers were associated with advanced fibrosis progression in NASH patients (OR 1.432 and 3.797 p < 0.01). Serum levels of IL-13 and C/C genotype in STAT6 rs167769 significantly increased the predictive capacity of serum AFP to predict HCC in F1–F2 and in F3–F4 fibrosis grades NASH patients. Conclusion: association between serum IL-13 and PD-L2 rs7854413 polymorphism successfully predict advanced fibrosis in NASH. However, HCC development in NASH is associated with higher serum AFP, IL-13 levels, and STAT6 rs167769, YAP1 rs11225163 polymorphisms.

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IL-13 receptor α2 is a negative prognostic factor in human lung cancer and stimulates lung cancer growth in mice

Cited by 30 publications

References 28 publications

IRS-1 increases TAZ expression and promotes osteogenic differentiation in rat bone marrow mesenchymal stem cells

IRS-1 increases TAZ expression and promotes osteogenic differentiation in rat bone marrow mesenchymal stem cells

Idiopathic Pulmonary Fibrosis and Lung Cancer: Mechanisms and Molecular Targets

Polymorphisms in Interleukin 13 Signaling and Interacting Genes Predict Advanced Fibrosis and Hepatocellular Carcinoma Development in Non-Alcoholic Steatohepatitis

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