Overexpression of STAT3 Potentiates Growth, Survival, and Radioresistance of Non-Small-Cell Lung Cancer (NSCLC) cells

Yin, Zhen-Jie; Jin, Fang; Liu, Tonggang; Fu, Enqing; Xie, Youhua; Sun, Rong

doi:10.1016/j.jss.2010.03.053

Cited by 52 publications

(35 citation statements)

References 26 publications

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“…These cells have been commonly used as a model in the mechanistic studies of lung cancer radiosensitivity [72–74], and they were cultured in RPMI-1640 medium with supplement of 10% fetal bovine serum (FBS, Gibco Invitrogen, Grand Island, NY, USA), 100 U/ml penicillin and 100 μg/ml streptomycin. All of the cells were cultured at 37°C in an atmosphere of 5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

Extracellular miR-1246 promotes lung cancer cell proliferation and enhances radioresistance by directly targeting DR5

Yuan

Wang

et al. 2016

Oncotarget

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MiRNAs in the circulation have been demonstrated to be a type of signaling molecule involved in intercellular communication but little is known about their role in regulating radiosensitivity. This study aims to investigate the effects of extracellular miRNAs induced by ionizing radiation (IR) on cell proliferation and radiosensitivity. The miRNAs in the conditioned medium (CM) from irradiated and non-irradiated A549 lung cancer cells were compared using a microarray assay and the profiles of 21 miRNAs up and down-regulated by radiation were confirmed by qRT-PCR. One of these miRNAs, miR-1246, was especially abundant outside the cells and had a much higher level compared with that inside of cells. The expressions of miR-1246 in both A549 and H446 cells increased along with irradiation dose and the time post-irradiation. By labeling exosomes and miR-1246 with different fluorescence dyes, it was found that the extracellular miR-1246 could shuttle from its donor cells to other recipient cells by a non-exosome associated pathway. Moreover, the treatments of cells with miR-1246 mimic or its antisense inhibitor showed that the extracellular miR-1246 could enhance the proliferation and radioresistance of lung cancer cells. A luciferase reporter-gene transfer experiment demonstrated that the death receptor 5 (DR5) was the direct target of miR-1246, and the kinetics of DR5 expression was opposite to that of miR-1246 in the irradiated cells. Our results show that the oncogene-like extracellular miR-1246 could act as a signaling messenger between irradiated and non-irradiated cells, more importantly, it contributes to cell radioresistance by directly suppressing the DR5 gene.

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Section: Methodsmentioning

confidence: 99%

Extracellular miR-1246 promotes lung cancer cell proliferation and enhances radioresistance by directly targeting DR5

Yuan

Wang

et al. 2016

Oncotarget

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“…JAKs are well-known to activate STAT signaling, leading to regulation of the gene expression that influences processes associated with tumor malignancy including cell-cycle progression, angiogenesis, metastasis, and immune evasion (17,18). Many investigations have demonstrated that JAKs and STATs are highly activated in cases of lung cancer and implied that JAKs as upstream regulators can be promising targets for lung cancer therapy (19,20). For this, smallmolecule compounds targeting JAKs and their signaling activity have been currently developed as chemotherapeutic reagents.…”

Section: Introductionmentioning

confidence: 99%

PAK1 Tyrosine Phosphorylation Is Required to Induce Epithelial–Mesenchymal Transition and Radioresistance in Lung Cancer Cells

et al. 2014

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The p21-activated Ser/Thr kinase 1 (PAK1) kinase has an essential role in tumorigenesis and cell survival in many cancers, but its regulation is not fully understood. In this study, we showed that in response to irradiation of lung cancer cells, PAK1 was upregulated, tyrosine phosphorylated, and translocated to the nucleus. Tyrosine phosphorylation relied upon JAK2 kinase activity and was essential for PAK1 protein stability and binding to Snail. This radiation-induced JAK2-PAK1-Snail signaling pathway increased epithelial-mesenchymal transition (EMT) by regulating epithelial and mesenchymal cell markers. Notably, JAK2 inhibitors mediated radiosensitization and EMT blockade in a mouse xenograft model of lung cancer. Taken together, our findings offered evidence that JAK2 phosphorylates and stabilizes functions of PAK1 that promote EMT and radioresistance in lung cancer cells, with additional implications for the use of JAK2 inhibitors as radiosensitizers in lung cancer treatment.

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“…It has been reported that overexpression of STAT3 is correlated with growth, survival, and radioresistance of NSCLC cells, and that STAT3 inhibition could inhibit tumorigenic ability and enhance the radiosensitivity of NSCLC cells both in vitro and in vivo (Yin et al, 2010;Hsu et al, 2011). Moreover, STAT3 polymorphisms have been shown to correlate with STAT3 expression and therapy response in certain malignancies (Ito et al, 2007;Kreil et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

STAT3 gene polymorphisms and susceptibility to non-small cell lung cancer

Jiang¹,

Zz²,

F³

et al. 2011

Genet. Mol. Res.

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ABSTRACT. Signal transducer and activator of transcription protein 3 (STAT3) has been implicated in cancer development and is recognized as a type of oncogene. However, association studies of single nucleotide polymorphisms (SNPs) in the STAT3 gene with cancer risk are rare and not available for lung cancer. We examined whether STAT3 polymorphisms are associated with the risk of non-small cell lung cancer (NSCLC). Eight SNPs in the STAT3 gene were genotyped by TaqMan assays in 326 NSCLC cases and 432 controls in a Chinese population. Significant decreased risk of NSCLC was observed for carriers of minor alleles rs4796793 (odds ratio (OR) = 0.68, 95% confidence interval (CI) = 0.51-0.

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Overexpression of STAT3 Potentiates Growth, Survival, and Radioresistance of Non-Small-Cell Lung Cancer (NSCLC) cells

Cited by 52 publications

References 26 publications

Extracellular miR-1246 promotes lung cancer cell proliferation and enhances radioresistance by directly targeting DR5

Extracellular miR-1246 promotes lung cancer cell proliferation and enhances radioresistance by directly targeting DR5

PAK1 Tyrosine Phosphorylation Is Required to Induce Epithelial–Mesenchymal Transition and Radioresistance in Lung Cancer Cells

STAT3 gene polymorphisms and susceptibility to non-small cell lung cancer

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