α,1,6-Fucosyltransferase (FUT8) regulates cancer-promoting capacities of cancer-associated fibroblasts (CAFs) through the modification of EGFR core fucosylation in non-small cell lung cancer

2019 ◽  
Author(s):  
Fengzhou Li ◽  
Shilei Zhao ◽  
Yanwei Cui ◽  
Jiaqi Qiang ◽  
Tao Guo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Microenvironment ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Normal Lung ◽  
Cancer Associated Fibroblasts ◽  
Small Cell Lung ◽  
Nsclc Patients

Abstract BackgroundCancer-associated fibroblasts (CAFs), the main component of the tumor microenvironment (TME) of NSCLC, are activated by phenotypic transformation into myofibroblasts. α,1,6-fucosyltransferase (FUT8), the key enzyme catalyzing core α,1,6-fucosylation (CF), plays important roles in multiple malignancies. In the current study, we investigated the functions and mechanism of CF mediated by FUT8 in CAFs in NSCLC through bioinformatics analysis, retrospective clinical studies and in vitro/in vivo laboratory experiments.MethodsBioinformatics was used to reveal the relationship between FUT8 and CAFs. Resected specimens, clinical data and prognostic information from 135 NSCLC patients were analyzed to assess the prognostic value of FUT8 in CAFs. Primary CAFs and normal lung fibroblasts were extracted from NSCLC patients and cocultured with NSCLC cell lines in a novel noncontact coculture device produced by 3D printing. In vivo, CAF/NSCLC coinjection tumorigenesis assay was performed in nude mice to study the function of FUT8/CF in TME. The mechanisms of FUT8/CF in CAFs regulating the cocultured NSCLC cells were investigated in cell and molecular experiments. ResultsFUT8 in CAFs is an independent risk factor for prognosis. FUT8/CF in CAFs is essential for CAFs to maintain their ability to promote NSCLC. FUT8/CF in CAFs is responsible for the cancer-promoting capacities of CAFs and lead to a malignant tumor microenvironment. CF modification enhances tyrosine phosphorylation of EGFR in CAFs, which causes activation of downstream signalings of EGFR and maintains cancer-promoting properties of CAFs.ConclusionFUT8 regulates cancer-promoting capacities of CAFs via the modification of EGFR CF in non-small cell lung cancer.

scholarly journals Epigenetic control of INSL4 promotes cell growth and invasiveness in Non-Small-Cell Lung Cancer

2020 ◽  
Author(s):  
Damiano Scopetti ◽  
Danilo Piobbico ◽  
Cinzia Brunacci ◽  
Stefania Pieroni ◽  
Guido Bellezza ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Growth ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Relaxin Family ◽  
Nsclc Patients

Abstract Background Non-Small Cell Lung Cancer accounts for 80–85% of all forms of Lung Cancer as leading cause of cancer-related death in human. Despite remarkable advances in the diagnosis and therapy of Lung Cancer, no significant improvements have thus far been achieved in terms of patients’ prognosis. Here, we investigated the role of INSL4 – a member of the relaxin family –in NSCLC.Methods We permanently overexpressed INSL4 in NSCLC cells in vitro to analyse the growth rate and the tumourigenic features. We further investigated the signalling pathways engaged in INSL4 overexpressing cells and the tumour growth ability by studying the tumour development in a patient derived tumour xenograft mouse model. Results We found a cell growth promoting effect by INSL4 overexpression in vitro in H1299 cells and in vivo in NOD/SCID mice. Surprisingly, in NSCLC-A549 cells, stable INSL4 overexpression has not showed similar effect, despite has an INSL4-mRNA expressed up to 22.000 fold more respect H1299. The INSL4-mRNA analysis of eight different NSCLC-derived cell lines, has revealed a great discrepancy between the amount of INSL4-mRNA and specific protein. Notably, similar result has been observed in studied NSCLC patients analysing and comparing INSL4 mRNA and protein expression. However, in a cohort of NSCLC patients, we found a significant inverse correlation between INSL4 expression and Overall Survival.Conclusions By combining the results from the in vitro and in vivo models and in silico analysis in patients whose NSCLCs adenocarcinoma spontaneously expressed high levels of INSL4 our results suggest that epigenetic modifications that affect INSL4 does not allow to assess precision therapy in selected patients without consider protein INSL4 amount.

scholarly journals Cross-Species Functional Analysis of Cancer-Associated Fibroblasts Identifies a Critical Role for CLCF1 and IL-6 in Non–Small Cell Lung Cancer In Vivo

2012 ◽  
Vol 72 (22) ◽  
pp. 5744-5756 ◽  
Author(s):  
Silvestre Vicent ◽  
Leanne C. Sayles ◽  
Dedeepya Vaka ◽  
Purvesh Khatri ◽  
Olivier Gevaert ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Functional Analysis ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Critical Role ◽  
Small Cell ◽  
Cancer Associated Fibroblasts ◽  
Small Cell Lung

Effect of friend leukemia virus integration 1 on tumorigenesis of small cell lung cancer cells and activation of the miR-17-92 pathway.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20015-e20015
Author(s):  
Jiuwei Cui ◽  
Lingyu Li ◽  
Wei Song ◽  
Jifan Hu ◽  
Wei Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Leukemia Virus ◽  
Small Cell ◽  
Normal Lung ◽  
Small Cell Lung ◽  
Friend Leukemia ◽  
Virus Integration

e20015 Background: Small cell lung cancer (SCLC) is regarded as the most devastative type of human lung malignancies, mostly due to their rapid and disseminated growth pattern. However, the molecular factors that drive rapid progression of SCLC remain unclear. Friend leukemia virus integration 1( FLI1),an Ets transcription factor family member, was identified as a proto-oncogene in some tumors via regulation of different target genes. In this study, we explored the potential role of FLI1 in SCLC. Methods: FLI1 protein expression was evaluated by immunohistochemistry in 67 primary SCLC, 20 non-small cell lung cancer (NSCLC) and 20 normal lung specimens. Correlation between FLI1 expression and clinical characteristics was evaluated with the logistic regression. Cell proliferation, cell cycle, apoptosis, colony formation assays in vitro and tumorigenesis assay in vivo were used to explore the function of FLI1 in SCLC cells. Use the miR-17-92 promoter/luciferase reporter assay to identify the regulation of FLI1 on miR-17-92 cluster promoter. Results: Immunohistochemical staining data showed that FLI1 was significantly upregulated in SCLC tissues compared to that in NSCLC and normal lung tissues ( p< 0.01). The expression score of FLI1 oncoprotein was associated with the extensive stage of SCLC and the overexpressed Ki67. Knockdown of FLI1 promoted apoptosis and induced repression of cell proliferation, tumor colony formation and in vivo tumorigenicity in highly aggressive SCLC cell lines. Importantly, we discovered that FLI1 promoted tumorigenesis by activating the miR-17-92 cluster family transcritption. Conclusions: This study uncovers that FLI1 is an important driving factor that promotes tumor growth in SCLC through the miR-17-92 pathway, and may serve as an attractive target for therapeutic intervention of SCLC.

scholarly journals Prognostic significance of CD276 in non-small cell lung cancer

Open Medicine ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. 805-812
Author(s):  
Changgong Zhang ◽  
Xuezhi Hao
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Expression Level ◽  
Normal Lung ◽  
Small Cell Lung ◽  
Nsclc Tissue ◽  
Normal Tissues ◽  
Nsclc Patients

AbstractBackgroundThe expression and significance of CD276 in non-small cell lung cancer (NSCLC) was explored.MethodThe BioGPS database was used to analyze the expression level of CD276 in normal tissues. Studies on the expression of CD276 in NSCLC patients using the Oncomine database. The prognostic roles of CD276 in NSCLC was studied using the Kaplan-Meier plotter database.ResultThe BioGPS database showed CD276 expression in all the human normal tissues. Compared with normal lung tissue, CD276 gene highly expressed in NSCLC tissue at mRNA level (P<0.05). The expression level of CD276 gene was negatively correlated with overall survival (OS) of NSCLC patients. Subgroup analysis showed that CD276 expression level had a significant effect on OS of patients with lung adenocarcinoma, while in squamous cell carcinoma its expression level had no significant effect on OS.ConclusionAccording to the information mined from the tumor gene database, CD276 mRNA was found highly expressed in NSCLC tissue and the expression of CD276 has a significant impact on survival of NSCLC patients, which provides an important theoretical basis for further study of the role of CD276 in the occurrence and development of NSCLC.

scholarly journals ALKBH4 promotes tumourigenesis with a poor prognosis in non-small-cell lung cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kentaro Jingushi ◽  
Masaya Aoki ◽  
Kazuhiro Ueda ◽  
Takahiro Kogaki ◽  
Masaya Tanimoto ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Poor Prognosis ◽  
Critical Role ◽  
Small Cell ◽  
Normal Lung ◽  
Small Cell Lung ◽  
And Function

AbstractThe human AlkB homolog family (ALKBH) of proteins play a critical role in some types of cancer. However, the expression and function of the lysine demethylase ALKBH4 in cancer are poorly understood. Here, we examined the expression and function of ALKBH4 in non-small-cell lung cancer (NSCLC) and found that ALKBH4 was highly expressed in NSCLC, as compared to that in adjacent normal lung tissues. ALKBH4 knockdown significantly induced the downregulation of NSCLC cell proliferation via cell cycle arrest at the G1 phase of in vivo tumour growth. ALKBH4 knockdown downregulated E2F transcription factor 1 (E2F1) and its target gene expression in NSCLC cells. ALKBH4 and E2F1 expression was significantly correlated in NSCLC clinical specimens. Moreover, patients with high ALKBH4 expression showed a poor prognosis, suggesting that ALKBH4 plays a pivotal tumour-promoting role in NSCLC.

scholarly journals Expression of long noncoding RNA NBAT1 is associated with the outcome of patients with non-small cell lung cancer

2020 ◽  
Vol 66 (7) ◽  
pp. 898-903
Author(s):  
Da-Ling Wang ◽  
Peng Yuan ◽  
Ji-Yuan Tian
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Prognostic Significance ◽  
Small Cell ◽  
Normal Lung ◽  
Small Cell Lung ◽  
Nsclc Patients

SUMMARY OBJECTIVE Long noncoding RNA neuroblastoma-associated transcript 1 (NBAT1) has been reported to be involved in cancer progression. However, the clinical significance of NBAT1 in non-small cell lung cancer (NSCLC) is still unclear. Our present research aimed to explore whether NBAT1 serves as a biomarker for NSCLC prognosis. METHODS The expression of NBAT1 was examined by RT-PCR in tissue samples of 162 NSCLC patients and was compared with the adjacent non-tumor lung specimens. Then the association between NBAT1 expression and clinical-pathological parameters was further evaluated. Survival analysis was performed using the Kaplan-Meier method. The prognostic significance of NBAT1 expression in NSCLC patients was explored by the use of univariate and multivariate analyses. RESULTS NBAT1 expression was prominently decreased in NSCLC tissues compared with matched normal lung specimens (p < 0.01). Moreover, survival analyses indicated that patients with low expression displayed dramatically decreased 5-year overall survival (p = 0.008). CONCLUSIONS NBAT1 expression might contribute to tumor progression and poor prognosis of NSCLC and might be a new therapeutic target in NSCLC.

scholarly journals Implications of the Adiponectin System in Non-Small Cell Lung Cancer Patients: A Case-Control Study

Biomolecules ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 926 ◽  
Author(s):  
Ersilia Nigro ◽  
Fabio Perrotta ◽  
Maria Ludovica Monaco ◽  
Rita Polito ◽  
Pia Clara Pafundi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adipose Tissue ◽  
Tumor Microenvironment ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Lung Tumor ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients ◽  
Healthy Lung

Alterations of adipose tissue occurring in obesity have been recognized as a major risk factor for several cancers. The relationship between adipose tissue and lung cancer, which is the main cancer-related cause of death worldwide, still requires investigation. Perturbations in the adipokine system are likely to interfere with inter-organ crosstalk in lung cancer, which may influence the lung tumor microenvironment. Adiponectin (Acrp30) expression is deregulated in several cancer types. Acrp30 circulates as oligomers with a Low (LMW), Medium (MMW), and High Molecular Weight (HMW), with the latter mediating the main biological effects. Acrp30 acts through AdipoR1 and AdipoR2 receptors. T-cadherin has been described as a non-signaling receptor. This study’s aim was to investigate the regulation of serum Acrp30 and its receptors in sample tissue from non-small cell lung cancer (NSCLC) patients. We recruited 72 NSCLC patients and 60 healthy controls, whom we evaluated in terms of their Acpr30 levels and oligomeric profile. In addition, the expression of AdipoRs in tissues from lung cancer specimens was also measured and compared to coupled healthy lung samples. Our findings show a significant reduction of total Acrp30 levels in NSCLC patients compared to normal subjects, with a specific down-regulation of HMW oligomers. Acrp30 expression was lower in lung adenocarcinoma than other subtypes, regardless of other factors. A significantly higher expression of AdipoR1 was observed, while no differences in R2 and a lower expression of T-cadherin were found in lung cancer specimens compared to normal healthy lung tissues. Involvement of the Acrp30 system in lung cancer may provide new insight into the interaction between adipose tissue and lung and sheds light on its potential ability to influence the lung tumor microenvironment.

Tumor-suppressive activity of sTRAIL on circulating CD44+ cells in patients with non-small cell lung cancer

2020 ◽  
Vol 401 (3) ◽  
pp. 417-422 ◽  
Author(s):  
Yan-Bin Sun ◽  
Guang-Hao Sun ◽  
Shun Xu ◽  
Jing-Jing Xu
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Enzyme Linked Immunosorbent Assay ◽  
Small Cell Lung ◽  
Healthy Control ◽  
Nsclc Patients

AbstractCirculating CD44+ cells have been identified as a prognostic marker for patients with non-small cell lung cancer (NSCLC). Serum tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) is involved in the pathophysiology of many cancers. However, no previous studies have shown the roles of sTRAIL in circulating CD44+ cells in the blood of NSCLC patients. We detected circulating CD44+ cells and sTRAIL levels in blood samples from NSCLC patients using flow cytometry and an enzyme-linked immunosorbent assay (ELISA). Anti-tumor roles of TRAIL in CD44+ cells were confirmed using a CCK-8 assay and mouse models. A higher number of circulating CD44+ cells were identified in NSCLC patients compared with healthy control individuals. In addition, we confirmed the anti-tumor roles and mechanisms of TRAIL in CD44+ cells both in vitro and in vivo. Our results indicate that (1) there is a negative correlation between sTRAIL and circulating CD44+ cells in NSCLC patients and (2) CD44+ cells have cancer stem cell properties and are more sensitive than CD44− cells to TRAIL.

scholarly journals Genetic Variants of CLPP and M1AP Are Associated With Risk of Non-Small Cell Lung Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Xianghan Li ◽  
Yiran Zou ◽  
Teng Li ◽  
Thomas K. F. Wong ◽  
Ryan T. Bushey ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Normal Lung ◽  
Advanced Stage ◽  
Small Cell Lung ◽  
Lung Cancer Patients ◽  
Nsclc Patients

BackgroundSingle nucleotide polymorphisms (SNPs) are often associated with distinct phenotypes in cancer. The present study investigated associations of cancer risk and outcomes with SNPs discovered by whole exome sequencing of normal lung tissue DNA of 15 non-small cell lung cancer (NSCLC) patients, 10 early stage and 5 advanced stage.MethodsDNA extracted from normal lung tissue of the 15 NSCLC patients was subjected to whole genome amplification and sequencing and analyzed for the occurrence of SNPs. The association of SNPs with the risk of lung cancer and survival was surveyed using the OncoArray study dataset of 85,716 patients (29,266 cases and 56,450 cancer-free controls) and the Prostate, Lung, Colorectal and Ovarian study subset of 1,175 lung cancer patients.ResultsWe identified 4 SNPs exclusive to the 5 patients with advanced stage NSCLC: rs10420388 and rs10418574 in the CLPP gene, and rs11126435 and rs2021725 in the M1AP gene. The variant alleles G of SNP rs10420388 and A of SNP rs10418574 in the CLPP gene were associated with increased risk of squamous cell carcinoma (OR = 1.07 and 1.07; P = 0.013 and 0.016, respectively). The variant allele T of SNP rs11126435 in the M1AP gene was associated with decreased risk of adenocarcinoma (OR = 0.95; P = 0.027). There was no significant association of these SNPs with the overall survival of lung cancer patients (P &gt; 0.05).ConclusionsSNPs identified in the CLPP and M1AP genes may be useful in risk prediction models for lung cancer. The previously established association of the CLPP gene with cancer progression lends relevance to our findings.

scholarly journals Long non-coding RNA SNHG14 exerts oncogenic functions in non-small cell lung cancer through acting as an miR-340 sponge

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Zhenhua Zhang ◽  
Yong Wang ◽  
Wei Zhang ◽  
Junyan Li ◽  
Weiliang Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cycle Arrest ◽  
Non Coding Rna ◽  
Nsclc Patients ◽  
Long Non Coding Rna

AbstractLong non-coding RNA (lncRNA) SNHG14 is previously found to be overexpressed in several types of cancers. However, the clinical significance and biological function of SNHG14 in non-small cell lung cancer (NSCLC) are still elusive. In the present study, we found that SNHG14 was aberrantly up-regulated in NSCLC tissues from patients and cell lines compared with their normal counterparts. Increased SNHG14 expression was closely associated with aggressive tumor progression and poor clinical outcome of NSCLC patients. Knockdown of SNHG14 inhibited NSCLC cell proliferation through inducing cell cycle arrest and apoptosis, whereas SNHG14 overexpression exerted the opposite effects. Animal experiment further revealed that down-regulated SNHG14 greatly inhibited NSCLC tumor growth in vivo. Further studies demonstrated that SNHG14 might serve as a competing endogenous RNA (ceRNA) by sponging miR-340 in NSCLC cells. Taken together, our study demonstrated that SNHG14/miR-340 axis might play a novel role in regulating the malignant behaviors of NSCLC, which provided a new potential diagnostic and therapeutic strategy for this malignant disease.

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