GXYLT2 accelerates cell growth and migration by regulating the Notch pathway in human cancer cells

Cui, Qi; Xing, Jinhao; Gu, Yajuan; Xu, Nan; Ma, Wenping; Chen, Yingyu; Zhao, Hongshan

doi:10.1016/j.yexcr.2019.01.023

Cited by 20 publications

(19 citation statements)

References 37 publications

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“…FERMT2 is a scaffolding protein that has been reported to promote the proliferation and migration of esophageal squamous cell carcinoma ( 74 ). GXYLT2 promotes the proliferation and migration of human cancer cells by regulating the NOTCH signaling pathway ( 75 ). SMPX is a small muscle protein located in the nucleus.…”

Section: Discussionmentioning

confidence: 99%

A Tumor Progression Related 7-Gene Signature Indicates Prognosis and Tumor Immune Characteristics of Gastric Cancer

et al. 2021

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BackgroundGastric cancer is a common gastrointestinal malignancy. Since it is often diagnosed in the advanced stage, its mortality rate is high. Traditional therapies (such as continuous chemotherapy) are not satisfactory for advanced gastric cancer, but immunotherapy has shown great therapeutic potential. Gastric cancer has high molecular and phenotypic heterogeneity. New strategies for accurate prognostic evaluation and patient selection for immunotherapy are urgently needed.MethodsWeighted gene coexpression network analysis (WGCNA) was used to identify hub genes related to gastric cancer progression. Based on the hub genes, the samples were divided into two subtypes by consensus clustering analysis. After obtaining the differentially expressed genes between the subtypes, a gastric cancer risk model was constructed through univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analysis. The differences in prognosis, clinical features, tumor microenvironment (TME) components and immune characteristics were compared between subtypes and risk groups, and the connectivity map (CMap) database was applied to identify potential treatments for high-risk patients.ResultsWGCNA and screening revealed nine hub genes closely related to gastric cancer progression. Unsupervised clustering according to hub gene expression grouped gastric cancer patients into two subtypes related to disease progression, and these patients showed significant differences in prognoses, TME immune and stromal scores, and suppressive immune checkpoint expression. Based on the different expression patterns between the subtypes, we constructed a gastric cancer risk model and divided patients into a high-risk group and a low-risk group based on the risk score. High-risk patients had a poorer prognosis, higher TME immune/stromal scores, higher inhibitory immune checkpoint expression, and more immune characteristics suitable for immunotherapy. Multivariate Cox regression analysis including the age, stage and risk score indicated that the risk score can be used as an independent prognostic factor for gastric cancer. On the basis of the risk score, we constructed a nomogram that relatively accurately predicts gastric cancer patient prognoses and screened potential drugs for high-risk patients.ConclusionsOur results suggest that the 7-gene signature related to tumor progression could predict the clinical prognosis and tumor immune characteristics of gastric cancer.

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Section: Discussionmentioning

confidence: 99%

A Tumor Progression Related 7-Gene Signature Indicates Prognosis and Tumor Immune Characteristics of Gastric Cancer

et al. 2021

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“…Overall, the importance of the Notch pathway for many aspects of development has clearly been demonstrated by numerous publications, and the pathway itself has been studied extensively. The Notch pathway is essential for many diseases, including Zika virus disease 26 , cardiovascular diseases 27 , Down syndrome 28 , and various cancer types [29][30][31] . Therefore, better understanding of the complex Notch pathway from all aspects are needed for potential therapeutic values.…”

Section: Discussionmentioning

confidence: 99%

Analysis of the Temporal Patterning of Notch Downstream Targets during Drosophila melanogaster Egg Chamber Development

Rowe

Paculis

Velasco-Tapia

et al. 2020

Sci Rep

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Living organisms require complex signaling interactions and proper regulation of these interactions to influence biological processes. Of these complex networks, one of the most distinguished is the Notch pathway. Dysregulation of this pathway often results in defects during organismal development and can be a causative mechanism for initiation and progression of cancer. Despite previous research entailing the importance of this signaling pathway and the organismal processes that it is involved in, less is known concerning the major Notch downstream targets, especially the onset and sequence in which they are modulated during normal development. As timing of regulation may be linked to many biological processes, we investigated and established a model of temporal patterning of major Notch downstream targets including broad, cut, and hindsight during Drosophila melanogaster egg chamber development. We confirmed the sequential order of Broad upregulation, Hindsight upregulation, and Cut downregulation. In addition, we showed that Notch signaling could be activated at stage 4, one stage earlier than the stage 5, a previously long-held belief. However, our further mitotic marker analysis restated that mitotic cycle continues until stage 5. Through our study, we once again validated the effectiveness and reliability of our MATLAB toolbox designed to systematically identify egg chamber stages based on area size, ratio, and additional morphological characteristics.

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“…Glucoside α3-xylosyltransferases (GXYLT1 and GXYLT2) and xyloside α3-xylosyltransferase (XXYLT1), for example, extend the O -glucose monosaccharides added by POGLUT1 [ 23 ]. Recent data has demonstrated that 70% or more of the NOTCH1 and NOTCH2 O -glucose glycoforms on 12 out of 17 EGF repeats are xylose-extended [ 24 ]. In mechanistic studies, the authors demonstrated that xylosyl extension by GXYLT1 and GXYLT2 is not necessary for the trafficking of endogenous NOTCH1 and NOTCH2 in HEK293T cells, while it is required for a proper protein trafficking in cells overexpressing NOTCH1 and NOTCH2 [ 24 ].…”

Section: From Golgi To the Cell Membranementioning

confidence: 99%

Targeting Notch Trafficking and Processing in Cancers

Pagliaro

Sissi

Roti

2020

Cells

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The Notch family comprises a group of four ligand-dependent receptors that control evolutionarily conserved developmental and homeostatic processes and transmit signals to the microenvironment. NOTCH undergoes remodeling, maturation, and trafficking in a series of post-translational events, including glycosylation, ubiquitination, and endocytosis. The regulatory modifications occurring in the endoplasmic reticulum/Golgi precede the intramembrane γ-secretase proteolysis and the transfer of active NOTCH to the nucleus. Hence, NOTCH proteins coexist in different subcellular compartments and undergo continuous relocation. Various factors, including ion concentration, enzymatic activity, and co-regulatory elements control Notch trafficking. Interfering with these regulatory mechanisms represents an innovative therapeutic way to bar oncogenic Notch signaling. In this review, we briefly summarize the role of Notch signaling in cancer and describe the protein modifications required for NOTCH to relocate across different subcellular compartments. We focus on the functional relationship between these modifications and the corresponding therapeutic options, and our findings could support the development of trafficking modulators as a potential alternative to the well-known γ-secretase inhibitors.

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GXYLT2 accelerates cell growth and migration by regulating the Notch pathway in human cancer cells

Cited by 20 publications

References 37 publications

A Tumor Progression Related 7-Gene Signature Indicates Prognosis and Tumor Immune Characteristics of Gastric Cancer

A Tumor Progression Related 7-Gene Signature Indicates Prognosis and Tumor Immune Characteristics of Gastric Cancer

Analysis of the Temporal Patterning of Notch Downstream Targets during Drosophila melanogaster Egg Chamber Development

Targeting Notch Trafficking and Processing in Cancers

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