Role of EGFL7/EGFR-signaling pathway in migration and invasion of growth hormone-producing pituitary adenomas

Liu, Qian; Zhang, Junwen; Gao, Hua; Yuan, Taoyang; Kang, Jie; Gui, Songbai; Zhang, Yazhou

doi:10.1007/s11427-018-9320-4

Cited by 18 publications

(30 citation statements)

References 29 publications

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“…6B) and EGFL7 were identified as both DMGs and DEGs. EGFL7 is reported to be a key factor for the regulation of the EGFR signaling pathway 46 . Additionally, EGFL7 is a secreted angiogenic factor that can result in pathologic angiogenesis and enhance tumor migration and invasion via the NOTCH signaling pathway 34 (a pathway enriched in the PPI-DMG network).…”

Section: Discussionmentioning

confidence: 99%

Integrative Network Analysis of Differentially Methylated and Expressed Genes for Biomarker Identification in Leukemia

Sanchez

Mackenzie

2020

Sci Rep

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Genome-wide DNA methylation and gene expression are commonly altered in pediatric acute lymphoblastic leukemia (PALL). Integrated network analysis of cytosine methylation and expression datasets has the potential to provide deeper insights into the complex disease states and their causes than individual disconnected analyses. With the purpose of identifying reliable cancer-associated methylation signal in gene regions from leukemia patients, we present an integrative network analysis of differentially methylated (DMGs) and differentially expressed genes (DEGs). The application of a novel signal detection-machine learning approach to methylation analysis of whole genome bisulfite sequencing (WGBS) data permitted a high level of methylation signal resolution in cancer-associated genes and pathways. This integrative network analysis approach revealed that gene expression and methylation consistently targeted the same gene pathways relevant to cancer: Pathways in cancer, Ras signaling pathway, PI3K-Akt signaling pathway, and Rap1 signaling pathway, among others. Detected gene hubs and hub sub-networks were integrated by signature loci associated with cancer that include, for example, NOTCH1, RAC1, PIK3CD, BCL2, and EGFR. Statistical analysis disclosed a stochastic deterministic relationship between methylation and gene expression within the set of genes simultaneously identified as DEGs and DMGs, where larger values of gene expression changes were probabilistically associated with larger values of methylation changes. Concordance analysis of the overlap between enriched pathways in DEG and DMG datasets revealed statistically significant agreement between gene expression and methylation changes. These results support the potential identification of reliable and stable methylation biomarkers at genes for cancer diagnosis and prognosis.Network-based modeling approaches have the potential to integrate and improve the perception of complex disease states and their root causes. To date, network analysis provides reliable and cost effective approaches for early disease detection, prediction of co-occurring diseases and interactions, and drug design 1 . Although integrated genomic analysis of methylation and gene expression in leukemia has been reported 2-5 , meaningful assimilation of network analysis is still lacking.Our study investigates protein-protein interaction networks (PPI), which are exclusively focused on protein-protein associations and resulting cell activities. A PPI network can be defined as a (un)directed graph/ network holding vertices as proteins (or protein-coding genes) and edges as the interactions/association between them. Associations are meant to be specific and biologically meaningful, i.e., two proteins are connected by an edge if jointly contributing to a shared function, which does not necessarily reflect a physical binding interaction.Within the network, some proteins denote hubs interacting with numerous partners. Biologically, hubs are key elements on which functionality of the cellular proces...

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Section: Discussionmentioning

confidence: 99%

Integrative Network Analysis of Differentially Methylated and Expressed Genes for Biomarker Identification in Leukemia

Sanchez

Mackenzie

2020

Sci Rep

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“…Previously, we found EGFL7 played the tumorigenesis role in pituitary adenomas [8][9]. Over-expression of EGFL7 is observed in growth hormone-producing pituitary adenomas [9] and prolactinoma [10].…”

Section: Introductionmentioning

confidence: 90%

“…This research studied the role c-myc played in EGFL7induced MMQ cell proliferation and PRL secretion in an effort to better understand the biological function of c-myc in the EGFL7 signaling pathway. Our previous investigation indicated that knockdown EGFL7 effectively inhibited pituitary adenoma cell growth [8][9] . In this study, MMQ cells were incubated with 50 ng/mL rhEGFL7 protein or PBS for 72 h. As shown in Figure 3, 50 ng/mL rhEGFL7 significantly promote cell proliferation ( Figure 3A, 1.88±0.37 fold) and PRL secretion ( Figure 3B, 1.51± 0.32 fold).…”

Section: Down Regulation C-myc Depress Egfl7 Induced Cell Proliferatimentioning

confidence: 99%

“…Tissue samples from 126 patients with prolactinomas were provided by the biobank of Beijing Neurosurgical Institute [8]. All these patients had an endoscopic trans-sphenoidal operation between December 2012 and January 2014 at Tiantan Hospital, Beijing, China.…”

Section: Patients and Specimensmentioning

confidence: 99%

“…Our previous results showed that the MAPK and PI3K/ AKT signaling pathway is a dominant driver in EGFL7 induced tumor growth and invasiveness [8,11]. Meanwhile, the PI3K/Akt and MAPK signaling cascades closely related to activation of c-myc [12].…”

Section: Introductionmentioning

confidence: 99%

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Anti-c-myc efficacy block EGFL7 induced prolactinoma tumorigenesis

Liu

Gao

et al. 2019

Open Chemistry

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Resistance to Dopamine agonists therapy is still a key factor that hinders the clinical treatment of prolactinoma. Consequently, a large number of investigations have been carried out to identify novel therapeutic targets. Our previous studies have suggested that the epidermal growth factor-like domain 7 (EGFL7) plays a crucial role in tumorigenesis of pituitary adenomas via EGFR/AKT/MAPK signaling pathway. In the present research, we found a positive staining of c-myc intimately associated with high-level EGFL7 in invasive prolactinoma compared to non-invasive prolactinoma and the normal pituitary gland. Meanwhile, PI3K/Akt and MAPK signaling cascades closely related to the activation of c-myc. Therefore, this research was conducted to explore the cooperation effect of c-myc and EGFL7 in prolactinoma. The inhibition of c-myc with anti-c-myc antibodies significantly reduced the proliferation, PRL secretion and invasion of rat prolactinoma MMQ cells. Notably, down regulation c-Myc by in vitro administration of anti-c-Myc antibodies could significantly depress EGFL7 induced MMQ cell proliferation, PRL secretion and invasion. An anti-c-Myc antibody could block EGFL7 induced Akt activation, but the expression of p-ERK was not altered by an anti-c-Myc antibody. Thus, our results suggest that anti-c-myc efficacy could block EGFL7 induced prolactinoma tumorigenesis via inhibited Akt activation in MMQ cells.

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Role of EGFL7 in human cancers: A review

de Oliveira,

Gonçalves,

Bidinotto

2023

Journal Cellular Physiology

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EGFL7 is a proangiogenic factor. It has been widely described with having a vital role in tubulogenesis and regulation of angiogenesis, mainly during embryogenesis and organogenesis. It has been mainly associated with NOTCH pathway, but there are reports showing association with MAPK and integrin pathways. Given its association with angiogenesis and these other pathways, there are several studies associating EGFL7 with carcinogenesis. In fact, most of the studies have pointed to EGFL7 as an oncogene, and some of them suggest EGFL7 expression as a possible biomarker of prognosis or use for a patient's follow‐up. Here, we review the molecular pathways which EGFL7 is associated and highlight several studies describing the role of EGFL7 in tumorigenesis, separated by tumor type. Besides its role on angiogenesis, EGFL7 may act in other pathways as oncogene, which makes it a possible biomarker and a candidate to targeted therapy.

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Role of EGFL7/EGFR-signaling pathway in migration and invasion of growth hormone-producing pituitary adenomas

Cited by 18 publications

References 29 publications

Integrative Network Analysis of Differentially Methylated and Expressed Genes for Biomarker Identification in Leukemia

Integrative Network Analysis of Differentially Methylated and Expressed Genes for Biomarker Identification in Leukemia

Anti-c-myc efficacy block EGFL7 induced prolactinoma tumorigenesis

Role of EGFL7 in human cancers: A review

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