Synergistic inhibition of cell migration by tetraspanin CD82 and gangliosides occurs via the EGFR or cMet-activated Pl3K/Akt signalling pathway

Li, Ying; Huang, Xiaohua; Zhang, Jianing; Li, Yuzhong; Ma, Keli

doi:10.1016/j.biocel.2013.08.002

Cited by 31 publications

(28 citation statements)

References 27 publications

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“…ADAM9 cleaved the pro-HB-EGF precursor to yield soluble HB-EGF, which binds to EGFR, thereby activating downstream signal transduction (26,41). The EGFR-AKT pathway is important for cell growth and migration (42,43). Our results showed that blocking ADAM9 inhibits EGFR-AKT activation by suppressing phosphorylation, but has no effect on ERK phosphorylation.…”

Section: Discussionmentioning

confidence: 69%

DNMT1–MicroRNA126 Epigenetic Circuit Contributes to Esophageal Squamous Cell Carcinoma Growth via ADAM9–EGFR–AKT Signaling

Liu

Jiang

et al. 2015

Clinical Cancer Research

100

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Purpose: MicroRNAs (miRNA) are involved in and are controlled by epigenetic regulation, and thereby form a reciprocal regulatory circuit. Using next-generation sequencing (NGS)-based miRNA profiling, this study aimed to discover esophageal squamous cell carcinoma (ESCC)-specific miRNAs and miRNArelated epigenetic modulations.Experimental Design: NGS-based miRNA profiles were generated for four pairs of ESCC tissues and adjacent normal tissues. In situ hybridization was used to assess miRNA expression and its correlation with prognosis. miRNA-related DNA methylations were identified using bisulfite genomic sequencing, and the role of DNA methyltransferase 1 (DNMT1) was investigated using RNA interference. miRNA targets were screened by mRNA sequencing, and functional validation was performed in vitro and in vivo.Results: NGS-based miRNA profiling identified 78 differentially expressed miRNAs in ESCC. Among them, microRNA126-3p (miR-126) was significantly downregulated, and its downregulation correlated with poor ESCC prognosis. Downregulation of miR-126 was due to promoter hypermethylation of its host gene, Egfl7. DNMT1 was aberrantly upregulated in ESCC and responsible for the hypermethylation of Egfl7. Intriguingly, DNMT1 was suppressed by overexpression of miR-126, indicating the existence of a regulatory feedback circuit. ADAM9 was identified as a key target of miR-126. Ectopic expression of miR-126 or silencing of ADAM9 reduced ESCC cell proliferation and migration by inhibiting epidermal growth factor receptor-AKT signaling.Conclusions: Our results indicate that miR-126 is a potential prognostic indicator for ESCC and suggest that a novel "DNMT1-miR-126 epigenetic circuit" is involved in ESCC progression. Consequently, miR-126-based epigenetic modulations may provide a basic rationale for new approaches to antitumor therapeutics.

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Section: Discussionmentioning

confidence: 69%

DNMT1–MicroRNA126 Epigenetic Circuit Contributes to Esophageal Squamous Cell Carcinoma Growth via ADAM9–EGFR–AKT Signaling

Liu

Jiang

et al. 2015

Clinical Cancer Research

100

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“…In CD82-expressing cells, GM2-and GM3-coated nanospheres exacerbate CD82-mediated inhibition of c-Met activation and cell migration [77]. The synergistically inhibitory effects of CD82 and GM3 or GM2/GM3 on the expression and/or activation of EGFR and c-Met are needed for CD82-mediated inhibition of EGF-or HGF-stimulated cell migration of HCCs [78]. CD82 undergoes lipid raft-dependent endocytosis, as sterol depletion from or sequestration in the plasma membrane markedly inhibits CD82 endocytosis, and CD82 endocytosis appears to alleviate CD82-mediated inhibition of cell migration [72].…”

Section: In Solid Tumor Cells Cd82 Regulates the Signaling Of Membramentioning

confidence: 97%

Tetraspanin CD82: a suppressor of solid tumors and a modulator of membrane heterogeneity

Feng

Huang

Wren

et al. 2015

Cancer Metastasis Rev

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Tetraspanin CD82 suppresses the progression and metastasis of a wide range of solid malignant tumors. However, its roles in tumorigenesis and hematopoietic malignancy remain unclear. Ubiquitously expressed CD82 restrains cell migration and cell invasion by modulating both cell-matrix and cell-cell adhesiveness and confining outside-in pro-motility signaling. This restraint at least contributes to, if not determines, the metastasis-suppressive activity and, also likely, the physiological functions of CD82. As a modulator of cell membrane heterogeneity, CD82 alters microdomains, trafficking, and topography of the membrane by changing the membrane molecular landscape. The functional activities of membrane molecules and the cytoskeletal interaction of the cell membrane are subsequently altered, followed by changes in cellular functions. Given its pathological and physiological importance, CD82 is a promising candidate for clinically predicting and blocking tumor progression and metastasis and also an emerging model protein for mechanistically understanding cell membrane organization and heterogeneity.

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“…The negative effect of G M3 was first demonstrated for EGFR signaling in a variety of cell lines including hepatoma, hepatocellular carcinoma and neuroblastoma cells [121,122,123,124]. G M3 inhibits the transition from inactive EGFR to signaling EGFR dimer, by preventing the autophosphorylation of the intracellular kinase domain in response to ligand binding.…”

Section: Regulation Of Ganglioside Expression By Pro-inflammatory mentioning

confidence: 99%

Role of Cytokine-Induced Glycosylation Changes in Regulating Cell Interactions and Cell Signaling in Inflammatory Diseases and Cancer

Dewald

Colomb

Bobowski-Gerard

et al. 2016

Cells

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Glycosylation is one of the most important modifications of proteins and lipids, and cell surface glycoconjugates are thought to play important roles in a variety of biological functions including cell-cell and cell-substrate interactions, bacterial adhesion, cell immunogenicity and cell signaling. Alterations of glycosylation are observed in number of diseases such as cancer and chronic inflammation. In that context, pro-inflammatory cytokines have been shown to modulate cell surface glycosylation by regulating the expression of glycosyltransferases involved in the biosynthesis of carbohydrate chains. These changes in cell surface glycosylation are also known to regulate cell signaling and could contribute to disease pathogenesis. This review summarizes our current knowledge of the glycosylation changes induced by pro-inflammatory cytokines, with a particular focus on cancer and cystic fibrosis, and their consequences on cell interactions and signaling.

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Synergistic inhibition of cell migration by tetraspanin CD82 and gangliosides occurs via the EGFR or cMet-activated Pl3K/Akt signalling pathway

Cited by 31 publications

References 27 publications

DNMT1–MicroRNA126 Epigenetic Circuit Contributes to Esophageal Squamous Cell Carcinoma Growth via ADAM9–EGFR–AKT Signaling

DNMT1–MicroRNA126 Epigenetic Circuit Contributes to Esophageal Squamous Cell Carcinoma Growth via ADAM9–EGFR–AKT Signaling

Tetraspanin CD82: a suppressor of solid tumors and a modulator of membrane heterogeneity

Role of Cytokine-Induced Glycosylation Changes in Regulating Cell Interactions and Cell Signaling in Inflammatory Diseases and Cancer

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