EphA4 promotes cell proliferation and cell adhesion–mediated drug resistance via the AKT pathway in multiple myeloma

Ding, Linlin; Shen, Yun; Ni, Jiazuan; Ou, Yiqing; Ou, Yangyu; Hong, Liu

doi:10.1177/1010428317694298

Cited by 19 publications

(15 citation statements)

References 32 publications

(45 reference statements)

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“…Overexpression of EPHA4 is reported in various carcinomas such as gastric cancer (Miyazaki et al, 2013) and pancreatic cancer (Liu et al, 2014). EPHA4 is a transmembrane receptor tyrosine kinase, which interacts with cyclin-dependent kinase 5 and enhances the expression of p-AKT (Ding et al, 2017). We identified hyperphosphorylation of EPHA4 at Y602 (3.6fold) in our data.…”

Section: Alteration Of Protein Kinases and Phosphatases In Cigarette supporting

confidence: 59%

Chronic Cigarette Smoke Mediated Global Changes in Lung Mucoepidermoid Cells: A Phosphoproteomic Analysis

Solanki

Advani

Khan

et al. 2017

OMICS: A Journal of Integrative Biology

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Proteomics analysis of chronic cigarette smoke exposure is a rapidly emerging postgenomics research field. While smoking is a major cause of lung cancer, functional studies using proteomics approaches could enrich our mechanistic understanding of the elusive lung cancer global molecular signaling and cigarette smoke relationship. We report in this study on a stable isotope labeling by amino acids in cell culture-based quantitative phosphoproteomic analysis of a human lung mucoepidermoid carcinoma cell line, H292 cells, chronically exposed to cigarette smoke. Using high resolution Orbitrap Velos mass spectrometer, we identified the hyperphosphorylation of 493 sites, which corresponds to 341 proteins and 195 hypophosphorylated sites, mapping to 142 proteins upon smoke exposure (2.0-fold change). We report differential phosphorylation of multiple kinases, including PAK6, EPHA4, LYN, mitogen-activated protein kinase, and phosphatases, including TMEM55B, PTPN14, TIGAR, among others, in response to chronic cigarette smoke exposure. Bioinformatics analysis revealed that the molecules differentially phosphorylated upon chronic exposure of cigarette smoke are associated with PI3K/AKT/mTOR and CDC42-PAK signaling pathways. These signaling networks are involved in multiple cellular processes, including cell polarity, cytoskeletal remodeling, cellular migration, protein synthesis, autophagy, and apoptosis. The present study contributes to emerging proteomics insights on cigarette smoke mediated global signaling in lung cells, which in turn may aid in development of precision medicine therapeutics and postgenomics biomarkers.

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Section: Alteration Of Protein Kinases and Phosphatases In Cigarette supporting

confidence: 59%

Chronic Cigarette Smoke Mediated Global Changes in Lung Mucoepidermoid Cells: A Phosphoproteomic Analysis

Solanki

Advani

Khan

et al. 2017

OMICS: A Journal of Integrative Biology

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“…The Eph receptor A4 ( EPHA4 ), a member of the erythropoietin‐producing hepatocellular (Eph) family, promotes cell adhesion of multiple myeloma cells by enhancing the phosphorylation levels of Akt probably due to its interaction with CDK5 . In our cellular system, the induction of EPHA4 in the hiPSC‐SLE line might influence the increase of pAkt levels .…”

Section: Discussionmentioning

confidence: 89%

Establishment and characterization of induced pluripotent stem cells (iPSCs) from central nervous system lupus erythematosus

Angelis

Santamaria

Parrotta

et al. 2019

J Cellular Molecular Medi

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Involvement of the central nervous system (CNS) is an uncommon feature in systemic lupus erythematosus (SLE), making diagnosis rather difficult and challenging due to the poor specificity of neuropathic symptoms and neurological symptoms. In this work, we used human‐induced pluripotent stem cells (hiPSCs) derived from CNS‐SLE patient, with the aim to dissect the molecular insights underlying the disease by gene expression analysis and modulation of implicated pathways. CNS‐SLE‐derived hiPSCs allowed us to provide evidence of Erk and Akt pathways involvement and to identify a novel cohort of potential biomarkers, namely CHCHD2, IDO1, S100A10, EPHA4 and LEFTY1, never reported so far. We further extended the study analysing a panel of oxidative stress‐related miRNAs and demonstrated, under normal or stress conditions, a strong dysregulation of several miRNAs in CNS‐SLE‐derived compared to control hiPSCs. In conclusion, we provide evidence that iPSCs reprogrammed from CNS‐SLE patient are a powerful useful tool to investigate the molecular mechanisms underlying the disease and to eventually develop innovative therapeutic approaches.

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“…Besides, it has been demonstrated that EPHA4 performs an important role in a lot of cellular processes, like promoting cell proliferation and cell adhesion-mediated drug resistance via the Akt signaling pathway [27]. While COL18A1 interacted with VTN and EPHA4, plays a crucial role in response of acute liver injury through binding α1β1 integrin on hepatocytes [28].…”

Section: Discussionmentioning

confidence: 99%

Proteomic Analysis for Identification of Novel Urinary Biomarkers in Juvenile Systemic Lupus Erythematosus

Zhang¹,

Cai

Zhi

et al. 2020

Preprint

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Background: To identify new markers of juvenile systemic lupus erythematosus (JSLE) that facilitate patient stratification and prognosis is quite important. Therefore, our aim of the present study is to analyze alteration of protein expression and potential valuable biomarkers in juvenile systemic lupus erythematosus (JSLE) urine. Methods: Based on this aim, proteomics assay analyzed the changes of urinary proteins in study groups consisting of 9 healthy controls, 9 inactive JSLE and 10 active JSLE patients. And the correlationship between clinical characteristics of JSLE patients and new biomarkers discovered from proteomics assay was qualified.Results: We have identified a group of 105 differentially expressed proteins with ≥1.3 fold up-regulation or ≤0.77 fold down-regulation in JSLE patients. In gene ontology and functional enrichment analysis, we discovered these proteins were involved in several important biological processes such as acute phase inflammatory responses, complement activation, hemostasis, and immune system regulation. Interestingly, we found that Ephrin type-A receptor 4 (EPHA4) and Vitronectin (VTN) were significantly reduced in the urine of both inactive and active JSLE patients. Especially, the urinary VTN was also linear correlated with clinical characteristics of JSLE. Conclusion: In summary, this study provided a reliable proteomic reference profile for JSLE. Patients with active and inactive JSLE have differentially obvious metabolic proteins in the urine. VTN could be a specific diagnostic biomarker to distinguish inactive and active JSLE. These identified proteins as new biomarkers in this study can warrant some further exploiting in a larger prospective validation study.

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EphA4 promotes cell proliferation and cell adhesion–mediated drug resistance via the AKT pathway in multiple myeloma

Cited by 19 publications

References 32 publications

Chronic Cigarette Smoke Mediated Global Changes in Lung Mucoepidermoid Cells: A Phosphoproteomic Analysis

Chronic Cigarette Smoke Mediated Global Changes in Lung Mucoepidermoid Cells: A Phosphoproteomic Analysis

Establishment and characterization of induced pluripotent stem cells (iPSCs) from central nervous system lupus erythematosus

Proteomic Analysis for Identification of Novel Urinary Biomarkers in Juvenile Systemic Lupus Erythematosus

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