Interleukin-6 stimulates aerobic glycolysis by regulating PFKFB3 at early stage of colorectal cancer

Han, Jun; Meng, Qingcai; Xi, Qiulei; Zhang, Yongxian; Zhuang, Qiulin; Han, Ying; Jiang, Yi; Ding, Qiurong; Wu, Guohao

doi:10.3892/ijo.2015.3225

Cited by 46 publications

(39 citation statements)

References 31 publications

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“…heterogeneity among the types of cancer may explain these differences. In addition, IL-6 overexpression can accelerate LNM in cervical cancer, colorectal cancer and lung cancer by stimulating cell proliferation, migration or EMT (36)(37)(38). This is consistent with the results from the present study, which demonstrated that IL-6 was upregulated and enriched in the PI3K-Akt signaling pathway, indicating that IL-6 may promote LNM progression in TC.…”

Section: Discussionsupporting

confidence: 92%

Integrated bioinformatics analysis to screen hub genes in the lymph node metastasis of thyroid cancer

Zhao

Shen

et al. 2019

Oncol Lett

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Thyroid cancer (TC) is one of the most common types of malignancy of the endocrine-system. At present, there is a lack of effective methods to predict neck lymph node metastasis (LNM) in TC. The present study compared the expression profiles from The Cancer Genome Atlas between N1M0 and N0M0 subgroups in each T1-4 stages TC in order to identify the four groups of TC LNM-associated differentially expressed genes (DEGs). Subsequently, DEGs were combined to obtain a total of 493 integrated DEGs by using the method of Robust Rank Aggregation. Furthermore, the underlying mechanisms of LNM were investigated. The results from Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses demonstrated that the identified DEGs may promote LNM via numerous pathways, including extracellular matrix-receptor interaction, PI3K-AKT signaling pathway and focal adhesion. Following construction of a protein-protein interaction network, the significance score for each gene was calculated and seven hub genes were screened, including interleukin 6, actinin α2, collagen type I α 1 chain, actin α1, calbindin 2, thrombospondin 1 and parathyroid hormone. These genes were predicted to serve crucial roles in TC with LNM. The results from the present study could therefore improve the understanding of LNM in TC. In addition, the seven DEGs identified may be considered as potential novel targets for the development of biomarkers that could be used in the diagnosis and therapy of TC.

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Section: Discussionsupporting

confidence: 92%

Integrated bioinformatics analysis to screen hub genes in the lymph node metastasis of thyroid cancer

Zhao

Shen

et al. 2019

Oncol Lett

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“…This is therefore a control point in the pathway and PFKFB3 is an acknowledged key regulator of glycolysis. Among the factors that trigger activation of PFKFB3 are inflammatory mediators; for example, IL‐6 increased PFKFB3 mRNA in mouse embryonic fibroblasts and cancer cell lines and several studies have indicated that LPS triggers PFKFB3 in macrophages . Few studies have investigated factors that drive PFKFB3 in microglia but we have reported that IFNγ alone and also LPS+Aβ exert this effect.…”

Section: Discussionmentioning

confidence: 87%

Iron accumulation in microglia triggers a cascade of events that leads to altered metabolism and compromised function in APP/PS1 mice

et al. 2019

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Among the changes that typify Alzheimer's disease (AD) are neuroinflammation and microglial activation, amyloid deposition perhaps resulting from compromised microglial function and iron accumulation. Data from Genome Wide Association Studies (GWAS) identified a number of gene variants that endow a significant risk of developing AD and several of these encode proteins expressed in microglia and proteins that are implicated in the immune response. This suggests that neuroinflammation and the accompanying microglial activation are likely to contribute to the pathogenesis of the disease. The trigger(s) leading to these changes remain to be identified. In this study, we set out to examine the link between the inflammatory, metabolic and iron-retentive signature of microglia in vitro and in transgenic mice that overexpress the amyloid precursor protein (APP) and presenilin 1 (PS1; APP/ PS1 mice), a commonly used animal model of AD. Stimulation of cultured microglia with interferon (IFN)γ and amyloid-β (Aβ) induced an inflammatory phenotype and switched the metabolic profile and iron handling of microglia so that the cells became glycolytic and iron retentive, and the phagocytic and chemotactic function of the cells was reduced. Analysis of APP/PS1 mice by magnetic resonance imaging (MRI) revealed genotype-related hypointense areas in the hippocampus consistent with iron deposition, and immunohistochemical analysis indicated that the iron accumulated in microglia, particularly in microglia that decorated Aβ deposits. Isolated microglia prepared from APP/PS1 mice were characterized by a switch to a glycolytic and iron-retentive phenotype and phagocytosis of Aβ was reduced in these cells. This evidence suggests that the switch to glycolysis in microglia may kick-start a cascade of events that ultimately leads to microglial dysfunction and Aβ accumulation.Brain Pathology 29 (2019) 606-621

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“…IL-6 is a critical tumour promoter during early CRC tumourigenesis[20]. In mice with colitis-associated cancer, anti-IL-6 receptor antibody treatment reduced the incidence of colitis-associated cancer (CAC) by decreasing the expression of key genes in aerobic glycolysis[23]. In an experimental CAC mouse model, researchers found that the expression levels of IL-6 protein were gradually increased after the induction of dysplastic lesions over time.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological significance of overexpression of interleukin-6 in colorectal cancer

Zeng

Tang

Liu

et al. 2017

WJG

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AIMTo compare the expression levels of interleukin (IL)-6 in colorectal cancer (CRC) tissues and adjacent non-cancerous tissues, and analyse the correlation of IL-6 expression with the clinicopathological parameters of CRC.METHODSFifty CRC tissue specimens and 50 matched adjacent mucosa specimens were collected. The expression of IL-6 in these clinical samples was examined by immunohistochemical staining. The correlation between IL-6 expression and clinicopathological parameters was assessed by statistical analysis.RESULTSIL-6 expression was significantly elevated in CRC tissues compared with noncancerous tissues (P < 0.001). IL-6 expression was positively correlated with tumour TNM stage (P < 0.001), but a negative correlation was detected between IL-6 expression and tumor histological differentiation in CRC (P < 0.05). Furthermore, IL-6 expression was associated with invasion depth and lymph node metastasis in CRC.CONCLUSIONIL-6 might be a useful marker for predicting a poor prognosis in patients with CRC and might be used as a potential therapeutic target in CRC.

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Interleukin-6 stimulates aerobic glycolysis by regulating PFKFB3 at early stage of colorectal cancer

Cited by 46 publications

References 31 publications

Integrated bioinformatics analysis to screen hub genes in the lymph node metastasis of thyroid cancer

Integrated bioinformatics analysis to screen hub genes in the lymph node metastasis of thyroid cancer

Iron accumulation in microglia triggers a cascade of events that leads to altered metabolism and compromised function in APP/PS1 mice

Clinicopathological significance of overexpression of interleukin-6 in colorectal cancer

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