The lectin concanavalin-A signals MT1-MMP catalytic independent induction of COX-2 through an IKKgamma/NF-kappaB-dependent pathway.
The lectin concanavalin-A signals MT1-MMP catalytic independent induction of COX-2 through an IKKgamma/NF-kappaB-dependent pathway.
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DOI：
10.1007/s12079-009-0084-0
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发表时间：
2010-03
影响因子：
4.1
通讯作者：
Annabi, Borhane
中科院分区：
文献类型：
--
作者：
Sina, Asmaa;Proulx-Bonneau, Sebastien;Roy, Alain;Poliquin, Laurent;Cao, Jian;Annabi, Borhane
The lectin from Canavalia ensiformis (Concanavalin-A, ConA), one of the most abundant lectins known, enables one to mimic biological lectin/carbohydrate interactions that regulate extracellular matrix protein recognition. As such, ConA is known to induce membrane type-1 matrix metalloproteinase (MT1-MMP) which expression is increased in brain cancer. Given that MT1-MMP correlated to high expression of cyclooxygenase (COX)-2 in gliomas with increasing histological grade, we specifically assessed the early proinflammatory cellular signaling processes triggered by ConA in the regulation of COX-2. We found that treatment with ConA or direct overexpression of a recombinant MT1-MMP resulted in the induction of COX-2 expression. This increase in COX-2 was correlated with a concomitant decrease in phosphorylated AKT suggestive of cell death induction, and was independent of MT1-MMP’s catalytic function. ConA- and MT1-MMP-mediated intracellular signaling of COX-2 was also confirmed in wild-type and in Nuclear Factor-kappaB (NF-κB) p65−/− mutant mouse embryonic fibroblasts (MEF), but was abrogated in NF-κB1 (p50)−/− and in I kappaB kinase (IKK) γ−/− mutant MEF cells. Collectively, our results highlight an IKK/NF-κB-dependent pathway linking MT1-MMP-mediated intracellular signaling to the induction of COX-2. That signaling pathway could account for the inflammatory balance responsible for the therapy resistance phenotype of glioblastoma cells, and prompts for the design of new therapeutic strategies that target cell surface carbohydrate structures and MT1-MMP-mediated signaling. Concise summary Concanavalin-A (ConA) mimics biological lectin/carbohydrate interactions that regulate the proinflammatory phenotype of cancer cells through yet undefined signaling. Here we highlight an IKK/NF-κB-dependent pathway linking MT1-MMP-mediated intracellular signaling to the induction of cyclooxygenase-2, and that could be responsible for the therapy resistance phenotype of glioblastoma cells.
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影响因子：
3.3
作者：
Korkolopoulou, Penelope;Levidou, Georgia;Patsouris, Efstratios
通讯作者：
Patsouris, Efstratios
影响因子：
12.4
作者：
通讯作者：
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DOI：
10.1038/sj.neo.7900034
发表时间：
1999-08-01
期刊：
Neoplasia (New York)
影响因子：
--
作者：
Berens, Michael E.;Giese, Alf
通讯作者：
Giese, Alf
影响因子：
12.7
作者：
Deininger, MH;Weller, M;Meyermann, R
通讯作者：
Meyermann, R
影响因子：
3.5
作者：
Fortier, Simon;Labelle, Dominique;Annabi, Borhane
通讯作者：
Annabi, Borhane