Annexin A6 inhibits Ras signalling in breast cancer cells

Muga, Sandra Vilà de; Timpson, Paul; Cubells, Laia; Evans, Rachael; Hayes, T E; Rentero, Carles; Hegemann, Anika; Reverter, Meritxell; Leschner, J; Pol, Albert; Tebar, Francesc; Daly, Roger J.; Enrich, Carlos; Grewal, Thomas

doi:10.1038/onc.2008.386

Cited by 65 publications

(127 citation statements)

References 66 publications

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“…Finally, we determined the secretion of tumor necrosis factor α (TNF-α) upon lipopolysaccharide (LPS) stimulation, which has been shown to require SNAP23 and syntaxin-4 (Kay et al , 2006; Manderson et al , 2007), using an enzyme-linked immunosorbent assay (ELISA)-based assay in A431 cells ± AnxA6 and in MDA-MB-436 and MDA-MB-468, two breast cancer cell lines characterized by high and low levels of AnxA6, respectively (Vila de Muga et al , 2009). In support of high AnxA6 levels inhibiting SNAP23/syntaxin-4–dependent exocytic pathways, secretion of TNF-α in A431wt cells was significantly higher compared with A431-A6 cells (Figure 10D).…”

Section: Resultsmentioning

confidence: 99%

“…Horseradish peroxidase–conjugated secondary antibodies were from Bio-Rad (Hercules, CA). The enhanced green fluorescent protein (EGFP)- and yellow fluorescent protein (YFP)-tagged caveolin-1 and AnxA6 expression vectors ± H- and K-Ras lipid anchors have been described elsewhere (Cubells et al , 2007; Monastyrskaya et al , 2009b; Vila de Muga et al , 2009). The NPC1-GFP was kindly provided by P. G. Pentchev (National Institutes of Health [NIH], Bethesda, MD).…”

Section: Methodsmentioning

confidence: 99%

“…The generation of the stable AnxA6-overexpressing CHO cell line (CHO-A6) and A431 cell line (A431-A6) has been described in detail (Grewal et al , 2000, 2005; Pons et al , 2001; Cubells et al , 2007; Vila de Muga et al , 2009). To generate AnxA6-overexpressing HuH7, we transfected HuH7 cells with pcDNAanx6 (Grewal et al , 2000) and selected in the presence of 1 mg/ml G418.…”

Section: Methodsmentioning

confidence: 99%

“…This includes the reorganization of the actin cytoskeleton at the plasma membrane (PM; Monastyrskaya et al , 2009b), the delivery of cholesterol from late endosomes to the Golgi and PM (Cubells et al , 2007), the cholesterol-dependent recruitment of cPLA 2 to the Golgi and its involvement in Golgi vesiculation (Cubells et al , 2008), as well as signal transduction events at the cell surface and possibly on endosomes (Grewal and Enrich, 2006; Vila de Muga et al , 2009). On cell activation, AnxA6 is predominantly targeted to the PM.…”

Section: Introductionmentioning

confidence: 99%

“…Follow-up studies revealed that reduced cholesterol availability in AnxA6-overexpressing cells perturbs cytosolic phospholipase A2 (cPLA 2 ) translocation to the Golgi, which is required to drive cholesterol-dependent vesiculation events (e.g., caveolin transport) from the Golgi apparatus (Cubells et al , 2008). This indirect role for AnxA6 in the secretory pathway and in membrane microdomain formation at the PM is most likely relevant for a large number of cells and tissues, as high amounts of AnxA6 are commonly found in most mammalian tissues, with the exception of undetectable to low AnxA6 levels in epithelial cells of the small intestine, parathyroid gland, and colon, as well as in several cell and mouse models of cancer (Vila de Muga et al , 2009; Grewal et al , 2010). …”

Section: Introductionmentioning

confidence: 99%

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Cholesterol transport from late endosomes to the Golgi regulates t-SNARE trafficking, assembly, and function

Reverter¹,

Rentero²,

Muga³

et al. 2011

Molecular Biology of the Cell

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This study shows that impaired cholesterol egress from late endosomes in cells with high annexin A6 levels is associated with altered soluble N-ethylmaleimide–sensitive fusion protein 23 (SNAP23) and syntaxin-4 cellular distribution and assembly and accumulation in Golgi membranes. This correlates with reduced secretion of cargo along the constitutive and SNAP23/syntaxin-4–dependent secretory pathway.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Cholesterol transport from late endosomes to the Golgi regulates t-SNARE trafficking, assembly, and function

Reverter¹,

Rentero²,

Muga³

et al. 2011

Molecular Biology of the Cell

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Annexin A6 is an organizer of membrane microdomains to regulate receptor localization and signalling

et al. 2011

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Annexin A6 (AnxA6) belongs to the conserved annexin protein family—a group of Ca2+‐dependent membrane binding proteins. It is the largest of all annexin proteins and upon activation, binds to negatively charged phospholipids in the plasma membrane and endosomes. In addition, AnxA6 associates with cholesterol‐rich membrane microdomains termed lipid rafts. Membrane cholesterol triggers Ca2+‐independent translocation of AnxA6 to membranes and AnxA6 levels determine the number of caveolae, a form of specialized rafts at the cell surface. AnxA6 also has an F‐actin binding domain and interacts with cytoskeleton components. Taken together, this suggests that AnxA6 has a scaffold function to link membrane microdomains with the organization of the cytoskeleton. Such a link facilitates AnxA6 to participate in plasma membrane repair and it would also impact on receptor signalling at the cell surface, growth factor, and lipoprotein receptor trafficking, Ca2+‐channel activity and T cell activation. Hence, the regulation of cell surface receptors by AnxA6 may be facilitated by its unique structure that allows recruitment of interaction partners and simultaneously bridging specialized membrane domains with cortical actin surrounding activated receptors. © 2011 IUBMB IUBMB Life, 63(11): 1009–1017, 2011

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Alterations of the podocyte proteome in response to high glucose concentrations

Schordan

Endlich

et al. 2009

Proteomics

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Diabetic nephropathy is one of the most common complications of diabetes mellitus and the leading cause of end-stage renal disease. A reduction in podocyte number has been documented in the kidneys of these patients. To identify the molecular changes in podocytes that are primarily caused by high glucose (HG) concentrations and not by secondary alterations (e.g. glomerular hypertension), we investigated the protein expression profiles in a podocyte cell line under long-term HG exposure (30 versus 10 mM for 2 wk). Proteins were separated by 2-DE, and we identified 39 different proteins in 48 spots that were differentially regulated by more than twofold in response to HG concentrations using MALDI-TOF MS and MASCOT software. These proteins belong to several protein classes, including cytoskeletal proteins and specific annexins (annexins III and VI). Downregulation of annexins III and VI by HG concentrations was confirmed by qRT-PCR, Western blot, and immunostaining, and was also observed in glomeruli of kidney biopsies from patients with diabetic nephropathy. Our data demonstrate that HG concentrations per se are sufficient to strongly modify the protein expression profile of podocytes, the analysis of which contributes to the identification of novel targets involved in diabetic nephropathy.

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Annexin A6 inhibits Ras signalling in breast cancer cells

Cited by 65 publications

References 66 publications

Cholesterol transport from late endosomes to the Golgi regulates t-SNARE trafficking, assembly, and function

Cholesterol transport from late endosomes to the Golgi regulates t-SNARE trafficking, assembly, and function

Annexin A6 is an organizer of membrane microdomains to regulate receptor localization and signalling

Alterations of the podocyte proteome in response to high glucose concentrations

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