PMID:22984561

Citation	Kotipatruni, RR, Nalla, AK, Asuthkar, S, Gondi, CS, Dinh, DH and Rao, JS (2012) Apoptosis Induced by Knockdown of uPAR and MMP-9 is Mediated by Inactivation of EGFR/STAT3 Signaling in Medulloblastoma. PLoS ONE 7:e44798
Abstract	Medulloblastoma is a highly invasive cancer of central nervous system diagnosed mainly in children. Matrix metalloproteinase-9 (MMP-9) and urokinase plasminogen activator receptor (uPAR) are over expressed in several cancers and well established for their roles in tumor progression. The present study is aimed to determine the consequences of targeting these molecules on medulloblastoma progression.
Links	PubMed Online version:10.1371/journal.pone.0044798
Keywords
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:UPAR		GO:0043066: negative regulation of apoptotic process	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Figure 1C and 1D show, through the Apo BrdU Assay and the Annexin-V assay, that inhibition of uPAR and MMP-9 induce apoptosis in Daoy and D283 cells.	complete CACAO 5685
HUMAN:UPAR		GO:0008637: apoptotic mitochondrial changes	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Figure 2B shows, through the transfection of Daoy and D283 cells, that downregulation of uPAR and MMP-9 reduces mitochondrial cytochrome C and Bak levels.	complete CACAO 5683
HUMAN:UPAR		GO:0045742: positive regulation of epidermal growth factor receptor signaling pathway	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Figure 4A shows that silencing uPAR and MMP-9 inhibits phosphorylation in the EGFR pathway.	complete CACAO 5036
HUMAN:UPAR		GO:0006916: anti-apoptosis	ECO:0000314: direct assay evidence used in manual assertion		P		Figure 1C and 1D show, through the Apo BrdU Assay and the Annexin-V assay, that inhibition of uPAR and MMP-9 induce apoptosis in Daoy and D283 cells.	complete CACAO 5085
HUMAN:UPAR		GO:0043388: positive regulation of DNA binding	ECO:0000314: direct assay evidence used in manual assertion		P		Figure 4C shows (through EMSA) that downregulation of uPAR and MMP-9 significantly inhibits binding activity of nuclear extract to STAT3 DNA probe.	complete CACAO 5180
HUMAN:UPAR		GO:0008633: obsolete activation of pro-apoptotic gene products	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Figure 2	complete CACAO 5198
HUMAN:UPAR		GO:0001934: positive regulation of protein phosphorylation	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Figure 4B shows, through pUM transfection, that silencing uPAR and MMP-9 significantly lowers the amount of phosphorylated STAT protein in the nucleus.	complete CACAO 5305
HUMAN:UPAR		GO:2001243: negative regulation of intrinsic apoptotic signaling pathway	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Figure 2 shows that downregulation of uPAR and MMP9 increases levels of gene products that induce apoptosis, showing that normal function negatively regulates apoptotic signaling pathways.	complete CACAO 5771
HUMAN:UPAR		GO:0090200: positive regulation of release of cytochrome c from mitochondria	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Figure 2 shows that downregulation of uPAR and MMP9 in medulloblastoma cells decreases the amount of cytosolic cytochrome c, indicating a reduction in release of cytochrome c from mitochondria.	complete CACAO 5870
HUMAN:UPAR		GO:0043154: negative regulation of cysteine-type endopeptidase activity involved in apoptotic process	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Fig. 3 showed that down regulation of uPAR and MMP9 in Daoy and D283 cells activates caspase activity. Synonym for negative regulation of caspase activity is negative regulation of cysteine-type endopeptidase activity involved in apoptotic process.	complete CACAO 6186
HUMAN:UPAR		GO:2001268: negative regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Fig. 3 showed that down regulation of uPAR and MMP9 in Daoy and D283 cells activates caspase activity.	complete CACAO 6190
HUMAN:MMP9		GO:0043066: negative regulation of apoptotic process	ECO:0000315:		P		Figure 1C and 1D show, through the Apo BrdU Assay and the Annexin-V assay, that inhibition of uPAR and MMP-9 induce apoptosis in Daoy and D283 cells.	complete CACAO 5686
HUMAN:MMP9	involved_in	GO:0043388: positive regulation of DNA binding	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:MMP9	involved_in	GO:2001268: negative regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:MMP9	involved_in	GO:0043066: negative regulation of apoptotic process	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:MMP9	involved_in	GO:0001934: positive regulation of protein phosphorylation	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:MMP9	involved_in	GO:0090200: positive regulation of release of cytochrome c from mitochondria	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:MMP9	involved_in	GO:2001243: negative regulation of intrinsic apoptotic signaling pathway	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:MMP9	involved_in	GO:0045742: positive regulation of epidermal growth factor receptor signaling pathway	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:MMP9		GO:0045742: positive regulation of epidermal growth factor receptor signaling pathway	ECO:0000315:		P		Figure 4A shows that silencing uPAR and MMP-9 significantly inhibits the phosphorylation of the EGFR pathway.	complete CACAO 5037
HUMAN:MMP9		GO:0043388: positive regulation of DNA binding	ECO:0000314:		P		Figure 4C shows (through EMSA) that downregulation of uPAR and MMP-9 significantly inhibits binding activity of nuclear extract to STAT3 DNA probe.	complete CACAO 5187
HUMAN:MMP9		GO:0008633: activation of pro-apoptotic gene products	ECO:0000315:		P		Figure 2	complete CACAO 5199
HUMAN:MMP9		GO:0001934: positive regulation of protein phosphorylation	ECO:0000315:		P		Figure 4B shows, through pUM transfection, that silencing uPAR and MMP-9 significantly lowers the amount of phosphorylated STAT protein in the nucleus.	complete CACAO 5306
HUMAN:MMP9		GO:2001243: negative regulation of intrinsic apoptotic signaling pathway	ECO:0000315:		P		Figure 2 shows that downregulation of uPAR and MMP9 increases levels of gene products that induce apoptosis, showing that normal function negatively regulates apoptotic signaling pathways.	complete CACAO 5772
HUMAN:MMP9		GO:0090200: positive regulation of release of cytochrome c from mitochondria	ECO:0000315:		P		Fig. 2 shows that downregulation of uPAR and MMP9 in Medulloblastoma cells causes a decrease in the amount of cytosolic cytochrome c, indicating a positive regulation of release of cytochrome c from mitochondria.	complete CACAO 5878
HUMAN:MMP9		GO:2001268: negative regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway	ECO:0000315:		P		Fig. 3 showed that down regulation of uPAR and MMP9 in Daoy and D283 cells activates caspase activity.	complete CACAO 6191
HUMAN:STAT3	involved_in	GO:0043066: negative regulation of apoptotic process	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

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