Publications by authors named "Abdallah Mound"

6 Publications

  • Page 1 of 1

Downregulation of type 3 inositol (1,4,5)-trisphosphate receptor decreases breast cancer cell migration through an oscillatory Ca signal.

Oncotarget 2017 Sep 18;8(42):72324-72341. Epub 2017 Aug 18.

Laboratory of Cellular and Molecular Physiology (EA-4667), "Ion Channels in Breast Cancer", SFR CAP-SANTE (FED-4231), University of Amiens, UFR Sciences, 80039 Amiens, France.

Breast cancer remains a research priority due to its invasive phenotype. Although the role of ion channels in cancer is now well established, the role of inositol (1,4,5)-trisphosphate (IP) receptors (IPRs) remains enigmatic. If the three IPRs subtypes expression have been identified in various cancers, little is known about their physiological role. Here, we investigated the involvement of IPR type 3 (IPR) in the migration processes of three human breast cancer cell lines showing different migration velocities: the low-migrating MCF-7 and the highly migrating and invasive MDA-MB-231 and MDA-MB-435S cell lines. We show that a higher IPR3 expression level, but not IPR1 nor IPR2, is correlated to a stronger cell line migration capacity and a sustained calcium signal. Interestingly, silencing of IPR3 highlights an oscillating calcium signaling profile and leads to a significant decrease of cell migration capacities of the three breast cancer cell lines. Conversely, stable overexpression of IPR3 in MCF-7 cells significantly increases their migration capacities. This effect is completely reversed by IPR3 silencing. In conclusion, we demonstrate that IPR3 expression level increases the migration capacity of human breast cancer cells by changing the calcium signature.
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http://dx.doi.org/10.18632/oncotarget.20327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5641133PMC
September 2017

Non-senescent keratinocytes organize in plasma membrane submicrometric lipid domains enriched in sphingomyelin and involved in re-epithelialization.

Biochim Biophys Acta Mol Cell Biol Lipids 2017 Sep 6;1862(9):958-971. Epub 2017 Jun 6.

URPHYM, Namur Research Institute for Life Sciences (NARILIS), University of Namur, Namur, Belgium. Electronic address:

Membrane lipid raft model has long been debated, but recently the concept of lipid submicrometric domains has emerged to characterize larger (micrometric) and more stable lipid membrane domains. Such domains organize signaling platforms involved in normal or pathological conditions. In this study, adhering human keratinocytes were investigated for their ability to organize such specialized lipid domains. Successful fluorescent probing of lipid domains, by either inserting exogenous sphingomyelin (BODIPY-SM) or using detoxified fragments of lysenin and theta toxins fused to mCherry, allowed specific, sensitive and quantitative detection of sphingomyelin and cholesterol and demonstrated for the first time submicrometric organization of lipid domains in living keratinocytes. Potential functionality of such domains was additionally assessed during replicative senescence, notably through gradual disappearance of SM-rich domains in senescent keratinocytes. Indeed, SM-rich domains were found critical to preserve keratinocyte migration before senescence, because sphingomyelin or cholesterol depletion in keratinocytes significantly alters lipid domains and reduce migration ability.
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http://dx.doi.org/10.1016/j.bbalip.2017.06.001DOI Listing
September 2017

Methyl-β-cyclodextrin treatment combined to incubation with interleukin-4 reproduces major features of atopic dermatitis in a 3D-culture model.

Arch Dermatol Res 2017 Jan 11;309(1):63-69. Epub 2016 Nov 11.

Research Unit for Molecular Physiology (URPhyM)-NARILIS, University of Namur, 61, rue de Bruxelles, B-5000, Namur, Belgium.

Atopic dermatitis (AD) skin is characterized by over-expression of interleukin (IL)-4, IL-13 and IL-25. When methyl-β-cyclodextrin (MβCD) treatment preceded exposure to these interleukins, combination of both treatments was found to mimic hallmarks of AD in vitro, such as barrier weakening, histological alterations and typical signaling responses in a reconstructed human epidermis (RHE). However, the respective role of each IL and whether any of them is critical when combined with MβCD treatment was unknown. Therefore, this work aimed to distinguish RHE responses after exposure to MβCD and each one of the three IL reported to mimic typical features of AD. IL-4 incubation preceded by MβCD was found responsible for altered histology, as well as for barrier alterations, evidenced by electrical resistance and dye permeation measurements. This combination further decreased loricrin (LOR) immunoreactivity, whereas mainly IL-25, combined to MβCD treatment, was able to downregulate filaggrin (FLG) mRNA level. Carbonic anhydrase II (CA2) and hyaluronan synthase 3 (HAS3), two other markers up-regulated in AD, were also induced when MβCD treatment was followed by IL-4, whilst the expression of neural epidermal growth factor-like 2 (NELL2) was up-regulated by paired IL-4 and IL-13. In conclusion, multiple features of AD were found in this in vitro model mainly when treatment of RHE by IL-4 was conducted after preliminary MβCD incubation.
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http://dx.doi.org/10.1007/s00403-016-1699-7DOI Listing
January 2017

Epidermal reference genes at the forefront of data interpretation.

Exp Dermatol 2015 Oct 21;24(10):738-9. Epub 2015 Aug 21.

URPHYM-Narilis, University of Namur, Namur, Belgium.

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http://dx.doi.org/10.1111/exd.12811DOI Listing
October 2015

Molecular interaction and functional coupling between type 3 inositol 1,4,5-trisphosphate receptor and BKCa channel stimulate breast cancer cell proliferation.

Eur J Cancer 2013 Nov 27;49(17):3738-51. Epub 2013 Aug 27.

Laboratory of Cellular and Molecular Physiology (EA-4667), 'Ion Channels in Breast Cancer', SFR CAP-SANTE (FED-4231), University of Amiens, UFR Sciences, 33 Rue Saint-Leu, 80039 Amiens, France.

Background: The implication of ion channels and inositol 1,4,5-trisphosphate (IP3)-induced Ca(2+) signalling (IICS) in the carcinogenesis processes, including deregulation of cell proliferation, migration and invasion, is increasingly studied. Studies from our laboratory have shown that type 3 IP3 receptor (IP3R3) and voltage- and Ca(2+)-dependent K(+) channels BKCa channels are involved in human breast cancer cell proliferation. In this context, we investigated the probable interaction between these two proteins (IP3R3 and BKCa channel) in normal and in breast cancer cells.

Methods: MCF-7 and MCF-10A cell viability was measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-assay in the presence or absence of adenosine triphosphate (ATP). Furthermore, cell-cycle analysis was carried out and cell cycle protein expression was examined by Western blotting. Immunocytochemistry and co-immunoprecipitation assays were used to check co-localisation of BKCa and IP3R3 and their molecular interaction. Finally, whole cell patch-clamp and Ca(2+) imaging were performed to assess the functional interaction.

Results: Our results are in favour of a functional and a molecular coupling between IP3R3 and BKCa channel that is involved in MCF-7 proliferation. Indeed, ATP increased MCF-7 cell proliferation and this effect was impaired when the expression of BKCa and/or IP3R3 has been reduced by specific small interfering RNAs (siRNAs). Flow cytometry experiments showed that both siRNAs led to cell cycle arrest in the G0/G1 phase and these results were confirmed by the analysis of cell cycle protein expression. Specifically, BKCa and IP3R3 silencing decreased both cyclin-D1 and cyclin-dependent kinase 4 (CDK4) expression levels. Furthermore, ATP elicited a phospholipase C (PLC)-dependent elevation of internal Ca(2+) that triggered in turn an iberiotoxin (IbTx)- and a tetra-ethyl-ammonium (TEA)-sensitive membrane hyperpolarisation that was strongly reduced in the cells with silenced IP3R3 or BKCa. In the same way, intracellular application of Ins(2,4,5)P3 triggered an IbTx-sensitive membrane hyperpolarisation. Moreover, intracellular Ca(2+) chelation with 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) prevented ATP-induced BKCa activation. BKCa and IP3R3 also co-immunoprecipitated and this interaction seemed to occur in cholesterol-enriched microdomains. Conversely, in the normal breast cell line MCF-10A, neither ATP application nor BKCa silencing affected cell proliferation. Furthermore, IP3R3 and BKCa did not co-immunoprecipitate, suggesting the absence of a molecular coupling between BKCa and IP3R3 in the MCF-10A normal cell line.

Conclusion: Altogether, our results suggest a molecular and functional link between BKCa channel and IP3R3 in cancer cells. Our findings led us to propose this coupling between BKCa and IP3R3 as an important mechanism for tumour cell proliferation.
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http://dx.doi.org/10.1016/j.ejca.2013.07.013DOI Listing
November 2013