PMID:22024282

Citation	Chetty, C, Vanamala, SK, Gondi, CS, Dinh, DH, Gujrati, M and Rao, JS (2012) MMP-9 induces CD44 cleavage and CD44 mediated cell migration in glioblastoma xenograft cells. Cell. Signal. 24:549-59
Abstract	CD44 is implicated in cell-cell and cell-matrix adhesion, cell migration, and signaling. CD44 cleavage correlates with the tumor burden and metastatic potential in various cancers. In this study, we demonstrate that matrix metalloproteinase-9 (MMP-9) acts as a processing enzyme for CD44 cleavage. Further, this processing event stimulates cell motility and inhibition of either CD44 or MMP-9 inhibited cell migration. MMP-9 and CD44 co-localization on the cell surface was observed in the histological sections of human glioblastoma (GBM) tissues. Confocal microscopy and co-immunoprecipitation studies in GBM xenograft cells further confirm this interaction. The interaction of MMP-9 with CD44 induced CD44 cleavage which was inhibited by both transcriptional knockdown of MMP-9 and with MMP-9 specific inhibitor. Further, supplementation of purified and activated human MMP-9 (hMMP-9) in MMP-9-knockdown cells resumed CD44 cleavage and migration. Additionally, activated hMMP-9 protein induced cleavage of recombinant human CD44 (rhCD44) in an in vitro assay. Selective overexpression of either extracellular domain (CD44(ECD)) or intracellular domain (CD44(ICD)) confirmed that CD44(ECD) played a role in cell migration and invasion. Taken together, our results suggest that MMP-9 is involved in the shedding of CD44 from cancer cells, which would promote the malignant potential of tumor cells.
Links	PubMed PMC3481542 Online version:10.1016/j.cellsig.2011.10.008
Keywords	Animals; Antigens, CD44/chemistry; Antigens, CD44/genetics; Antigens, CD44/metabolism; Cell Line, Tumor; Cell Membrane/drug effects; Cell Membrane/genetics; Cell Membrane/metabolism; Cell Movement/drug effects; Cell Movement/genetics; Enzyme Activation; Enzyme Inhibitors/pharmacology; Gene Expression; Gene Knockdown Techniques; Glioblastoma/genetics; Glioblastoma/metabolism; Glioblastoma/pathology; Humans; Immunoprecipitation; Matrix Metalloproteinase 9/deficiency; Matrix Metalloproteinase 9/genetics; Matrix Metalloproteinase 9/pharmacology; Matrix Metalloproteinase Inhibitors; Mice; Neoplasm Invasiveness/genetics; Protein Structure, Tertiary; Proteolysis; RNA, Small Interfering/genetics; RNA, Small Interfering/metabolism; Signal Transduction/drug effects; Transplantation, Heterologous
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:MMP9		GO:0008237: metalloendopeptidase activity	ECO:0000315:		F		Figure 4a-c MMP-9 induces cleavage of CD44 into the extracellular domain and the intracellular domain in 4910 and 5310 xenograft cells. The interaction of MMP-9 with CD44 induced CD44 cleavage which was inhibited by both transcriptional knockdown of MMP-9 and with MMP-9 specific inhibitor. Further, supplementation of purified and activated human MMP-9 (hMMP-9) in MMP-9-knockdown cells resumed CD44 cleavage and migration. Additionally, activated hMMP-9 protein induced cleavage of recombinant human CD44.	complete CACAO 12123

References

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