G-CSF Promotes Neuroblastoma Tumorigenicity and Metastasis via STAT3-Dependent Cancer Stem Cell Activation

Agarwal, Saurabh; Lakoma, Anna; Chen, Zaowen; Hicks, John; Metelitsa, Leonid S.; Kim, Eugene; Shohet, Jason M.

doi:10.1158/0008-5472.can-14-2946

Cited by 82 publications

(88 citation statements)

References 51 publications

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“…CSF1-CSF1R activation can trigger several important signaling pathways, such as the PI3K–AKT and STAT3 pathways [15–17], most of which regulate cell proliferation, invasion, and inflammation. Therefore, we investigated the possibility that miR- 1207-5p regulates those pathways by targeting CSF1 .…”

Section: Resultsmentioning

confidence: 99%

miR-1207-5p suppresses lung cancer growth and metastasis by targeting CSF1

et al. 2016

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We previously reported that miR-1207-5p can inhibit epithelial-mesenchymal transition (EMT) induced by growth factors such as EGF and TGF-β, but the exact mechanism is unclear. Here we identified that Colony stimulating factor 1 (CSF1) is a target gene of miR-1207-5p. CSF1 controls the production, differentiation and function of macrophage and promotes the release of proinflammatory chemokines. We showed that miR-1207-5p inhibited lung cancer cell A549 proliferation, migration and invasion in vitro, and suppressed the STAT3 and AKT signalings. miR-1207-5p overexpression can increase HUVEC angiogenesis, and can modulate the M2 phenotype of macrophage. miR-1207-5p also significantly inhibited A549 cells metastasis in a nude mouse xenograft model. miR-1207-5p and CSF1 expression levels and their relationship with lung cancer survival and metastasis status were assayed by means of a lung cancer tissue microarray. Macrophage is an essential part of the tumor microenvironment, thus the miR-1207-5p-CSF1 axis maybe a new regulator of lung cancer development through modulating the tumor microenvironment.

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Section: Resultsmentioning

confidence: 99%

miR-1207-5p suppresses lung cancer growth and metastasis by targeting CSF1

et al. 2016

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“…Of which, CSF3R , which is a member of the family of cytokine receptors and may also function in some cell surface adhesion or recognition processes, was reported to be related to tumor growth and metastasis [25]. MSH2 , a component of the post-replicative DNA mismatch repair system, frequently mutated in melanoma brain metastases but not in primary melanomas, indicating the high genomic instability of metastatic samples [26].…”

Section: Resultsmentioning

confidence: 99%

Characterization of RNA editome in primary and metastatic lung adenocarcinomas

et al. 2016

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RNA editing results in post-transcriptional modification and could potentially contribute to carcinogenesis. However, RNA editing in advanced lung adenocarcinomas has not yet been studied. Based on whole genome and transcriptome sequencing data, we identified 1,071,296 RNA editing events from matched normal, primary and metastatic samples contributed by 24 lung adenocarcinoma patients, with 91.3% A-to-G editing on average, and found significantly more RNA editing sites in tumors than in normal samples. To investigate cancer relevant editing events, we detected 67,851 hyper-editing sites in primary and 50,480 hyper-editing sites in metastatic samples. 46 genes with hyper-editing in coding regions were found to result in amino acid alterations, while hundreds of hyper-editing events in non-coding regions could modulate splicing or gene expression, including genes related to tumor stage or clinic prognosis. Comparing RNA editome of primary and metastatic samples, we also discovered hyper-edited genes that may promote metastasis development. These findings showed a landscape of RNA editing in matched normal, primary and metastatic tissues of lung adenocarcinomas for the first time and provided new insights to understand the molecular characterization of this disease.

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“…Several studies demonstrate that activation of STAT3 by IL-6 produced by BM-MSC plays a key role in EMDR in NB (10,21). Likewise, activation of STAT3 by G-CSF also directly negatively impacts chemosensitivity of NB cells (22). However, as a transcription factor, direct STAT3 targeting is difficult, especially for clinical translation.…”

Section: Introductionmentioning

confidence: 99%

Sphingosine-1-Phosphate Receptor-1 Promotes Environment-Mediated and Acquired Chemoresistance

Lifshitz

Priceman

et al. 2017

Molecular Cancer Therapeutics

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Drug resistance is a major barrier for the development of effective and durable cancer therapies. Overcoming this challenge requires further defining the cellular and molecular mechanisms underlying drug resistance, both acquired and environment-mediated drug resistance (EMDR). Here, using neuroblastoma (NB), a childhood cancer with high incidence of recurrence due to resistance to chemotherapy, as a model we show that human bone marrow-mesenchymal stromal cells induce tumor expression of sphingosine-1-phosphate receptor-1 (S1PR1) leading to their resistance to chemotherapy. Targeting S1PR1 by shRNA markedly enhances etoposide-induced apoptosis in NB cells and abrogates EMDR, while over-expression of S1PR1 significantly protects NB cells from multidrug-induced apoptosis via activating JAK-STAT3 signaling. Elevated S1PR1 expression and STAT3 activation are also observed in human NB cells with acquired resistance to etoposide. We show in vitro and in human NB xenograft models that treatment with FTY720, an FDA-approved drug and antagonist of S1PR1, dramatically sensitizes drug-resistant cells to etoposide. In summary, we identify S1PR1 as a critical target for reducing both EMDR and acquired chemoresistance in NB.

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G-CSF Promotes Neuroblastoma Tumorigenicity and Metastasis via STAT3-Dependent Cancer Stem Cell Activation

Cited by 82 publications

References 51 publications

miR-1207-5p suppresses lung cancer growth and metastasis by targeting CSF1

miR-1207-5p suppresses lung cancer growth and metastasis by targeting CSF1

Characterization of RNA editome in primary and metastatic lung adenocarcinomas

Sphingosine-1-Phosphate Receptor-1 Promotes Environment-Mediated and Acquired Chemoresistance

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