Involvement of ROS-alpha v beta 3 integrin-FAK/Pyk2 in the inhibitory effect of melatonin on U251 glioma cell migration and invasion under hypoxia

Xu, Congcong; Wang, Xinghuan; Huang, Xiao-Dong; Dai, Liming; Cao, Changjun; Li, Zhiqiang

doi:10.1186/s12967-015-0454-8

Cited by 53 publications

(35 citation statements)

References 51 publications

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“…Under hypoxic conditions in a glioma model (U251 lineage), inhibition of αvβ3 integrin decreased focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (Pyk2) phosphorylation, which are associated with cell migration and invasion [186]. …”

Section: Alterations In the Cell–cell And Cell–extracellular Matrix Imentioning

confidence: 99%

Glycobiology Modifications in Intratumoral Hypoxia: The Breathless Side of Glycans Interaction

Silva-filho¹,

Sena²,

Lima

et al. 2017

Cell Physiol Biochem

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Post-translational and co-translational enzymatic addition of glycans (glycosylation) to proteins, lipids, and other carbohydrates, is a powerful regulator of the molecular machinery involved in cell cycle, adhesion, invasion, and signal transduction, and is usually seen in both in vivo and in vitro cancer models. Glycosyltransferases can alter the glycosylation pattern of normal cells, subsequently leading to the establishment and progression of several diseases, including cancer. Furthermore, a growing amount of research has shown that different oxygen tensions, mainly hypoxia, leads to a markedly altered glycosylation, resulting in altered glycan-receptor interactions. Alteration of intracellular glucose metabolism, from aerobic cellular respiration to anaerobic glycolysis, inhibition of integrin 3α1β translocation to the plasma membrane, decreased 1,2-fucosylation of cell-surface glycans, and galectin overexpression are some consequences of the hypoxic tumor microenvironment. Additionally, increased expression of gangliosides carrying N-glycolyl sialic acid can also be significantly affected by hypoxia. For all these reasons, it is possible to realize that hypoxia strongly alters glycobiologic events within tumors, leading to changes in their behavior. This review aims to analyze the complexity and importance of glycoconjugates and their molecular interaction network in the hypoxic context of many solid tumors.

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Section: Alterations In the Cell–cell And Cell–extracellular Matrix Imentioning

confidence: 99%

Glycobiology Modifications in Intratumoral Hypoxia: The Breathless Side of Glycans Interaction

Silva-filho¹,

Sena²,

Lima

et al. 2017

Cell Physiol Biochem

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“…Glioblastoma has strong activity of migration and invasion [2], which is associated to low oxygen condition of tumor microenvironment [4][5][6]. Thus it's essential to find a way to block hypoxia-induced migration and invasion.…”

Section: Discussionmentioning

confidence: 99%

“…This aggressive phenotype is possibly relevant to hypoxia, which is one of the most remarkably characteristics of glioma microenvironment and might play a crucial role in glioma growth, development, and angiogenesis [3]. It has been documented that hypoxia also induces migration and invasion of glioma cells [4][5][6], which involves a series of transduction pathways and signal molecules.…”

mentioning

confidence: 99%

Resveratrol inhibits hypoxia-induced glioma cell migration and invasion by the p-STAT3/miR-34a axis

Wang¹,

Han²,

Zhang³

2016

neo

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Hypoxia promotes aggressiveness, angiogenesis and resistance in glioma. It has been reported that resveratrol has strong anti-tumor ability and can inhibit migration and invasion of varieties of tumor including glioma. However, whether resveratrol inhibits hypoxia-induced migration and invasion of glioma cells is still unknown. In this study, we found glioma U87 and U251 cells migration and invasion was reduced by resveratrol under hypoxia condition and higher doses led to stronger block, while proliferation of U87 and U251 cells was hardly effected. Mechanically, hypoxia-induced upregulation of phosphorylated signal transducer and activator of transcription 3(p-STAT3) was blocked by resveratrol. MicroRNA-34a (miR-34a) is a tumor suppressor whose promoter region has a conserved STAT3-binding site and can be negatively regulated by STAT3. Interestingly, miR-34a was downregulated under hypoxia but upregulated by resveratrol which was perhaps relevant to changes in level of p-STAT3. The effect of resveratrol on p-STAT3 and miR-34a was both time-and dose-dependent. Summarizing, resveratrol inhibits hypoxia-induced migration and invasion possibly via p-STAT3/miR-34a axis and this effect is both time-and dose-dependent.

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“…The complex interplay between solid tumors and host melatonergic microenvironment has been studied in several cancers. For example, melatonin contributes to the cross talk between cell‐cell and cell‐matrix adhesion by reducing the expression of α v β 3 integrin, which limits glioma cell migration into surrounding stroma . Additionally, melatonin participates in the reduction of surrounding fibroblasts and endothelial cells by downregulating antiadipogenic cytokine expression in breast cancer .…”

Section: Introductionmentioning

confidence: 99%

“…For example, melatonin contributes to the cross talk between cell-cell and cell-matrix adhesion by reducing the expression of α v β 3 integrin, which limits glioma cell migration into surrounding stroma. 8 Additionally, melatonin participates in the reduction of surrounding fibroblasts and endothelial cells by downregulating antiadipogenic cytokine expression in breast cancer. 9 However, the majority of these studies were performed on tumor cells or animal models; little has been done to observe the effects of the melatonergic system in patients with malignant diseases.…”

Section: Introductionmentioning

confidence: 99%

Pan‐cancer genomic analyses reveal prognostic and immunogenic features of the tumor melatonergic microenvironment across 14 solid cancer types

Lv¹,

Zheng²,

Wang³

et al. 2019

Journal of Pineal Research

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We performed comprehensive genomic analyses of the melatonergic system within the tumor microenvironment and their clinical relevance across a broad spectrum of solid tumors. RNA‐seq data from The Cancer Genome Atlas (TCGA) of 14 solid tumors representing 6658 human samples were analyzed. The tumor melatonergic system was characterized by the rates of melatonin synthesis and metabolism using a two‐gene expression model (melatonin synthesis/metabolism Index). We calculated three indexes according to different melatonin metabolism isoenzymes (Index‐I [ASMT:CYP1A1], Index‐II [ASMT:CYP1A2], and Index‐III [ASMT:CYP1B1]). Samples of each cancer type were classified into two subgroups (high vs low) based on median values. Clinical outcomes, mutational burden, and neoepitope abundance were analyzed and compared. We found that the ability of the tumor microenvironment to synthesize and accumulate melatonin varied across cancer types and negatively correlated with tumor burden. Kaplan‐Meier survival analyses and multivariable modeling showed that the three indexes played different roles across different cancers and harbored prognostic values in breast cancer (adjusted hazard ratio [AHR]Index‐II = 0.65 [0.44‐0.97]; P = 0.03), cervical cancer (AHRIndex‐I = 0.62 [0.39‐0.98]; P = 0.04), lung squamous cell carcinoma (AHRIndex‐III = 0.75 [0.56‐0.99]; P = 0.04), melanoma (AHRIndex‐I = 0.74 [0.55‐0.98]; P = 0.04), and stomach adenocarcinoma (AHRIndex‐III = 0.68 [0.41‐0.94]; P = 0.02). We further investigated its clinical relevance with tumor immunogenic features (mutational burden and neoantigen abundance), which may predict immunotherapy benefits. We observed significant negative correlations with mutational burden in the majority of tumors (P < 0.05), except cervical cancer, pancreatic adenocarcinoma, and thyroid carcinoma. Our study provides a systematic overview of the oncostatic values of the melatonergic system and highlights the utilization of this simple and promising gene signature as a prognosticator and potential predictor of response to immunotherapy.

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Involvement of ROS-alpha v beta 3 integrin-FAK/Pyk2 in the inhibitory effect of melatonin on U251 glioma cell migration and invasion under hypoxia

Cited by 53 publications

References 51 publications

Glycobiology Modifications in Intratumoral Hypoxia: The Breathless Side of Glycans Interaction

Glycobiology Modifications in Intratumoral Hypoxia: The Breathless Side of Glycans Interaction

Resveratrol inhibits hypoxia-induced glioma cell migration and invasion by the p-STAT3/miR-34a axis

Pan‐cancer genomic analyses reveal prognostic and immunogenic features of the tumor melatonergic microenvironment across 14 solid cancer types

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