PubMed:19306381 JSONTXT

{"project":"LitCoin-sentences","denotations":[{"id":"T1","span":{"begin":0,"end":139},"obj":"Sentence"},{"id":"T2","span":{"begin":140,"end":268},"obj":"Sentence"},{"id":"T3","span":{"begin":269,"end":406},"obj":"Sentence"},{"id":"T4","span":{"begin":407,"end":482},"obj":"Sentence"},{"id":"T5","span":{"begin":483,"end":689},"obj":"Sentence"},{"id":"T6","span":{"begin":690,"end":927},"obj":"Sentence"},{"id":"T7","span":{"begin":928,"end":1168},"obj":"Sentence"},{"id":"T8","span":{"begin":1169,"end":1348},"obj":"Sentence"},{"id":"T9","span":{"begin":1349,"end":1508},"obj":"Sentence"},{"id":"T10","span":{"begin":1509,"end":1636},"obj":"Sentence"},{"id":"T11","span":{"begin":1637,"end":1877},"obj":"Sentence"},{"id":"T12","span":{"begin":1878,"end":2015},"obj":"Sentence"}],"text":"Neuregulin-1 beta and neuregulin-1 alpha differentially affect the migration and invasion of malignant peripheral nerve sheath tumor cells.\nMalignant peripheral nerve sheath tumors (MPNSTs) are the most common malignancy associated with neurofibromatosis Type 1 (NF1). These Schwann cell lineage-derived sarcomas aggressively invade adjacent nerve and soft tissue, frequently precluding surgical resection. Little is known regarding the mechanisms underlying this invasive behavior. We have shown that MPNSTs express neuregulin-1 (NRG-1) beta isoforms, which promote Schwann cell migration during development, and NRG-1 alpha isoforms, whose effects on Schwann cells are poorly understood. Hypothesizing that NRG-1 beta and/or NRG-1 alpha promote MPNST invasion, we found that NRG-1 beta promoted MPNST migration in a substrate-specific manner, markedly enhancing migration on laminin but not on collagen type I or fibronectin. The NRG-1 receptors erbB3 and erbB4 were present in MPNST invadopodia (processes mediating invasion), partially colocalized with focal adhesion kinase and the laminin receptor beta(1)-integrin and coimmunoprecipitated with beta(1)-integrin. NRG-1 beta stimulated human and murine MPNST cell migration and invasion in a concentration-dependent manner in three-dimensional migration assays, acting as a chemotactic factor. Both baseline and NRG-1 beta-induced migration were erbB-dependent and required the action of MEK 1/2, SAPK/JNK, PI-3 kinase, Src family kinases and ROCK-I/II. In contrast, NRG-1 alpha had no effect on the migration and invasion of some MPNST lines and inhibited the migration of others. While NRG-1 beta potently and persistently activated Erk 1/2, SAPK/JNK, Akt and Src family kinases, NRG-1 alpha did not activate Akt and activated these other kinases with kinetics distinct from those evident in NRG-1 beta-stimulated cells. These findings suggest that NRG-1 beta enhances MPNST migration and that NRG-1 beta and NRG-1 alpha differentially modulate this process."}

{"project":"LitCoin-entities-OrganismTaxon-PD","denotations":[{"id":"T1","span":{"begin":1191,"end":1196},"obj":"OrganismTaxon"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"NCBItxid:9606"}],"text":"Neuregulin-1 beta and neuregulin-1 alpha differentially affect the migration and invasion of malignant peripheral nerve sheath tumor cells.\nMalignant peripheral nerve sheath tumors (MPNSTs) are the most common malignancy associated with neurofibromatosis Type 1 (NF1). These Schwann cell lineage-derived sarcomas aggressively invade adjacent nerve and soft tissue, frequently precluding surgical resection. Little is known regarding the mechanisms underlying this invasive behavior. We have shown that MPNSTs express neuregulin-1 (NRG-1) beta isoforms, which promote Schwann cell migration during development, and NRG-1 alpha isoforms, whose effects on Schwann cells are poorly understood. Hypothesizing that NRG-1 beta and/or NRG-1 alpha promote MPNST invasion, we found that NRG-1 beta promoted MPNST migration in a substrate-specific manner, markedly enhancing migration on laminin but not on collagen type I or fibronectin. The NRG-1 receptors erbB3 and erbB4 were present in MPNST invadopodia (processes mediating invasion), partially colocalized with focal adhesion kinase and the laminin receptor beta(1)-integrin and coimmunoprecipitated with beta(1)-integrin. NRG-1 beta stimulated human and murine MPNST cell migration and invasion in a concentration-dependent manner in three-dimensional migration assays, acting as a chemotactic factor. Both baseline and NRG-1 beta-induced migration were erbB-dependent and required the action of MEK 1/2, SAPK/JNK, PI-3 kinase, Src family kinases and ROCK-I/II. In contrast, NRG-1 alpha had no effect on the migration and invasion of some MPNST lines and inhibited the migration of others. While NRG-1 beta potently and persistently activated Erk 1/2, SAPK/JNK, Akt and Src family kinases, NRG-1 alpha did not activate Akt and activated these other kinases with kinetics distinct from those evident in NRG-1 beta-stimulated cells. These findings suggest that NRG-1 beta enhances MPNST migration and that NRG-1 beta and NRG-1 alpha differentially modulate this process."}

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beta and neuregulin-1 alpha differentially affect the migration and invasion of malignant peripheral nerve sheath tumor cells.\nMalignant peripheral nerve sheath tumors (MPNSTs) are the most common malignancy associated with neurofibromatosis Type 1 (NF1). These Schwann cell lineage-derived sarcomas aggressively invade adjacent nerve and soft tissue, frequently precluding surgical resection. Little is known regarding the mechanisms underlying this invasive behavior. We have shown that MPNSTs express neuregulin-1 (NRG-1) beta isoforms, which promote Schwann cell migration during development, and NRG-1 alpha isoforms, whose effects on Schwann cells are poorly understood. Hypothesizing that NRG-1 beta and/or NRG-1 alpha promote MPNST invasion, we found that NRG-1 beta promoted MPNST migration in a substrate-specific manner, markedly enhancing migration on laminin but not on collagen type I or fibronectin. The NRG-1 receptors erbB3 and erbB4 were present in MPNST invadopodia (processes mediating invasion), partially colocalized with focal adhesion kinase and the laminin receptor beta(1)-integrin and coimmunoprecipitated with beta(1)-integrin. NRG-1 beta stimulated human and murine MPNST cell migration and invasion in a concentration-dependent manner in three-dimensional migration assays, acting as a chemotactic factor. Both baseline and NRG-1 beta-induced migration were erbB-dependent and required the action of MEK 1/2, SAPK/JNK, PI-3 kinase, Src family kinases and ROCK-I/II. In contrast, NRG-1 alpha had no effect on the migration and invasion of some MPNST lines and inhibited the migration of others. While NRG-1 beta potently and persistently activated Erk 1/2, SAPK/JNK, Akt and Src family kinases, NRG-1 alpha did not activate Akt and activated these other kinases with kinetics distinct from those evident in NRG-1 beta-stimulated cells. These findings suggest that NRG-1 beta enhances MPNST migration and that NRG-1 beta and NRG-1 alpha differentially modulate this process."}

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{"project":"LitCoin-GeneOrGeneProduct-v3","denotations":[{"id":"T1","span":{"begin":0,"end":10},"obj":"GeneOrGeneProduct"},{"id":"T2","span":{"begin":22,"end":32},"obj":"GeneOrGeneProduct"},{"id":"T3","span":{"begin":35,"end":40},"obj":"GeneOrGeneProduct"},{"id":"T4","span":{"begin":120,"end":126},"obj":"GeneOrGeneProduct"},{"id":"T5","span":{"begin":167,"end":173},"obj":"GeneOrGeneProduct"},{"id":"T6","span":{"begin":237,"end":261},"obj":"GeneOrGeneProduct"},{"id":"T7","span":{"begin":263,"end":266},"obj":"GeneOrGeneProduct"},{"id":"T8","span":{"begin":517,"end":527},"obj":"GeneOrGeneProduct"},{"id":"T9","span":{"begin":531,"end":536},"obj":"GeneOrGeneProduct"},{"id":"T10","span":{"begin":614,"end":619},"obj":"GeneOrGeneProduct"},{"id":"T11","span":{"begin":620,"end":625},"obj":"GeneOrGeneProduct"},{"id":"T12","span":{"begin":709,"end":714},"obj":"GeneOrGeneProduct"},{"id":"T13","span":{"begin":727,"end":732},"obj":"GeneOrGeneProduct"},{"id":"T14","span":{"begin":733,"end":738},"obj":"GeneOrGeneProduct"},{"id":"T15","span":{"begin":777,"end":782},"obj":"GeneOrGeneProduct"},{"id":"T16","span":{"begin":877,"end":884},"obj":"GeneOrGeneProduct"},{"id":"T17","span":{"begin":896,"end":904},"obj":"GeneOrGeneProduct"},{"id":"T18","span":{"begin":915,"end":926},"obj":"GeneOrGeneProduct"},{"id":"T19","span":{"begin":932,"end":937},"obj":"GeneOrGeneProduct"},{"id":"T20","span":{"begin":948,"end":953},"obj":"GeneOrGeneProduct"},{"id":"T21","span":{"begin":958,"end":963},"obj":"GeneOrGeneProduct"},{"id":"T22","span":{"begin":1057,"end":1078},"obj":"GeneOrGeneProduct"},{"id":"T23","span":{"begin":1087,"end":1103},"obj":"GeneOrGeneProduct"},{"id":"T24","span":{"begin":1104,"end":1120},"obj":"GeneOrGeneProduct"},{"id":"T25","span":{"begin":1151,"end":1167},"obj":"GeneOrGeneProduct"},{"id":"T26","span":{"begin":1169,"end":1174},"obj":"GeneOrGeneProduct"},{"id":"T27","span":{"begin":1367,"end":1372},"obj":"GeneOrGeneProduct"},{"id":"T28","span":{"begin":1443,"end":1448},"obj":"GeneOrGeneProduct"},{"id":"T29","span":{"begin":1452,"end":1456},"obj":"GeneOrGeneProduct"},{"id":"T30","span":{"begin":1462,"end":1473},"obj":"GeneOrGeneProduct"},{"id":"T31","span":{"begin":1475,"end":1493},"obj":"GeneOrGeneProduct"},{"id":"T32","span":{"begin":1498,"end":1504},"obj":"GeneOrGeneProduct"},{"id":"T33","span":{"begin":1522,"end":1527},"obj":"GeneOrGeneProduct"},{"id":"T34","span":{"begin":1528,"end":1533},"obj":"GeneOrGeneProduct"},{"id":"T35","span":{"begin":1643,"end":1648},"obj":"GeneOrGeneProduct"},{"id":"T36","span":{"begin":1690,"end":1697},"obj":"GeneOrGeneProduct"},{"id":"T37","span":{"begin":1699,"end":1703},"obj":"GeneOrGeneProduct"},{"id":"T38","span":{"begin":1709,"end":1712},"obj":"GeneOrGeneProduct"},{"id":"T39","span":{"begin":1717,"end":1735},"obj":"GeneOrGeneProduct"},{"id":"T40","span":{"begin":1737,"end":1742},"obj":"GeneOrGeneProduct"},{"id":"T41","span":{"begin":1743,"end":1748},"obj":"GeneOrGeneProduct"},{"id":"T42","span":{"begin":1766,"end":1769},"obj":"GeneOrGeneProduct"},{"id":"T43","span":{"begin":1849,"end":1854},"obj":"GeneOrGeneProduct"},{"id":"T44","span":{"begin":1906,"end":1911},"obj":"GeneOrGeneProduct"},{"id":"T45","span":{"begin":1951,"end":1956},"obj":"GeneOrGeneProduct"},{"id":"T46","span":{"begin":1966,"end":1971},"obj":"GeneOrGeneProduct"},{"id":"T47","span":{"begin":1972,"end":1977},"obj":"GeneOrGeneProduct"}],"text":"Neuregulin-1 beta and neuregulin-1 alpha differentially affect the migration and invasion of malignant peripheral nerve sheath tumor cells.\nMalignant peripheral nerve sheath tumors (MPNSTs) are the most common malignancy associated with neurofibromatosis Type 1 (NF1). These Schwann cell lineage-derived sarcomas aggressively invade adjacent nerve and soft tissue, frequently precluding surgical resection. Little is known regarding the mechanisms underlying this invasive behavior. We have shown that MPNSTs express neuregulin-1 (NRG-1) beta isoforms, which promote Schwann cell migration during development, and NRG-1 alpha isoforms, whose effects on Schwann cells are poorly understood. Hypothesizing that NRG-1 beta and/or NRG-1 alpha promote MPNST invasion, we found that NRG-1 beta promoted MPNST migration in a substrate-specific manner, markedly enhancing migration on laminin but not on collagen type I or fibronectin. The NRG-1 receptors erbB3 and erbB4 were present in MPNST invadopodia (processes mediating invasion), partially colocalized with focal adhesion kinase and the laminin receptor beta(1)-integrin and coimmunoprecipitated with beta(1)-integrin. NRG-1 beta stimulated human and murine MPNST cell migration and invasion in a concentration-dependent manner in three-dimensional migration assays, acting as a chemotactic factor. Both baseline and NRG-1 beta-induced migration were erbB-dependent and required the action of MEK 1/2, SAPK/JNK, PI-3 kinase, Src family kinases and ROCK-I/II. In contrast, NRG-1 alpha had no effect on the migration and invasion of some MPNST lines and inhibited the migration of others. While NRG-1 beta potently and persistently activated Erk 1/2, SAPK/JNK, Akt and Src family kinases, NRG-1 alpha did not activate Akt and activated these other kinases with kinetics distinct from those evident in NRG-1 beta-stimulated cells. These findings suggest that NRG-1 beta enhances MPNST migration and that NRG-1 beta and NRG-1 alpha differentially modulate this process."}

{"project":"LitCoin_Mondo_095","denotations":[{"id":"T1","span":{"begin":93,"end":132},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T4","span":{"begin":140,"end":180},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T7","span":{"begin":182,"end":188},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T8","span":{"begin":210,"end":220},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T9","span":{"begin":237,"end":254},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T10","span":{"begin":263,"end":266},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T11","span":{"begin":352,"end":356},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T12","span":{"begin":502,"end":508},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T13","span":{"begin":747,"end":752},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T14","span":{"begin":797,"end":802},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T15","span":{"begin":980,"end":985},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T16","span":{"begin":1208,"end":1213},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T17","span":{"begin":1586,"end":1591},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T18","span":{"begin":1926,"end":1931},"obj":"DiseaseOrPhenotypicFeature"}],"attributes":[{"id":"A9","pred":"mondo_id","subj":"T9","obj":"0018975"},{"id":"A11","pred":"mondo_id","subj":"T11","obj":"0013894"},{"id":"A10","pred":"mondo_id","subj":"T10","obj":"0018975"},{"id":"A16","pred":"mondo_id","subj":"T16","obj":"0017827"},{"id":"A18","pred":"mondo_id","subj":"T18","obj":"0017827"},{"id":"A12","pred":"mondo_id","subj":"T12","obj":"0017827"},{"id":"A7","pred":"mondo_id","subj":"T7","obj":"0017827"},{"id":"A8","pred":"mondo_id","subj":"T8","obj":"0004992"},{"id":"A17","pred":"mondo_id","subj":"T17","obj":"0017827"},{"id":"A4","pred":"mondo_id","subj":"T4","obj":"0017827"},{"id":"A5","pred":"mondo_id","subj":"T4","obj":"0004545"},{"id":"A6","pred":"mondo_id","subj":"T4","obj":"0004345"},{"id":"A15","pred":"mondo_id","subj":"T15","obj":"0017827"},{"id":"A14","pred":"mondo_id","subj":"T14","obj":"0017827"},{"id":"A1","pred":"mondo_id","subj":"T1","obj":"0017827"},{"id":"A2","pred":"mondo_id","subj":"T1","obj":"0004545"},{"id":"A3","pred":"mondo_id","subj":"T1","obj":"0004345"},{"id":"A13","pred":"mondo_id","subj":"T13","obj":"0017827"}],"text":"Neuregulin-1 beta and neuregulin-1 alpha differentially affect the migration and invasion of malignant peripheral nerve sheath tumor cells.\nMalignant peripheral nerve sheath tumors (MPNSTs) are the most common malignancy associated with neurofibromatosis Type 1 (NF1). These Schwann cell lineage-derived sarcomas aggressively invade adjacent nerve and soft tissue, frequently precluding surgical resection. Little is known regarding the mechanisms underlying this invasive behavior. We have shown that MPNSTs express neuregulin-1 (NRG-1) beta isoforms, which promote Schwann cell migration during development, and NRG-1 alpha isoforms, whose effects on Schwann cells are poorly understood. Hypothesizing that NRG-1 beta and/or NRG-1 alpha promote MPNST invasion, we found that NRG-1 beta promoted MPNST migration in a substrate-specific manner, markedly enhancing migration on laminin but not on collagen type I or fibronectin. The NRG-1 receptors erbB3 and erbB4 were present in MPNST invadopodia (processes mediating invasion), partially colocalized with focal adhesion kinase and the laminin receptor beta(1)-integrin and coimmunoprecipitated with beta(1)-integrin. NRG-1 beta stimulated human and murine MPNST cell migration and invasion in a concentration-dependent manner in three-dimensional migration assays, acting as a chemotactic factor. Both baseline and NRG-1 beta-induced migration were erbB-dependent and required the action of MEK 1/2, SAPK/JNK, PI-3 kinase, Src family kinases and ROCK-I/II. In contrast, NRG-1 alpha had no effect on the migration and invasion of some MPNST lines and inhibited the migration of others. While NRG-1 beta potently and persistently activated Erk 1/2, SAPK/JNK, Akt and Src family kinases, NRG-1 alpha did not activate Akt and activated these other kinases with kinetics distinct from those evident in NRG-1 beta-stimulated cells. These findings suggest that NRG-1 beta enhances MPNST migration and that NRG-1 beta and NRG-1 alpha differentially modulate this process."}

{"project":"LitCoin-MeSH-Disease-2","denotations":[{"id":"T1","span":{"begin":93,"end":132},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T2","span":{"begin":140,"end":180},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T3","span":{"begin":182,"end":188},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T4","span":{"begin":210,"end":220},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T5","span":{"begin":237,"end":261},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T6","span":{"begin":263,"end":266},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T7","span":{"begin":304,"end":312},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T8","span":{"begin":502,"end":508},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T9","span":{"begin":747,"end":752},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T10","span":{"begin":797,"end":802},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T11","span":{"begin":980,"end":985},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T12","span":{"begin":1208,"end":1213},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T13","span":{"begin":1586,"end":1591},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T14","span":{"begin":1926,"end":1931},"obj":"DiseaseOrPhenotypicFeature"}],"attributes":[{"id":"A10","pred":"ID:","subj":"T10","obj":"D018319"},{"id":"A7","pred":"ID:","subj":"T7","obj":"D012509"},{"id":"A8","pred":"ID:","subj":"T8","obj":"D018319"},{"id":"A11","pred":"ID:","subj":"T11","obj":"D018319"},{"id":"A14","pred":"ID:","subj":"T14","obj":"D018319"},{"id":"A4","pred":"ID:","subj":"T4","obj":"D009369"},{"id":"A12","pred":"ID:","subj":"T12","obj":"D018319"},{"id":"A3","pred":"ID:","subj":"T3","obj":"D018319"},{"id":"A13","pred":"ID:","subj":"T13","obj":"D018319"},{"id":"A5","pred":"ID:","subj":"T5","obj":"D009456"},{"id":"A9","pred":"ID:","subj":"T9","obj":"D018319"},{"id":"A2","pred":"ID:","subj":"T2","obj":"D018319"},{"id":"A1","pred":"ID:","subj":"T1","obj":"D018319"},{"id":"A6","pred":"ID:","subj":"T6","obj":"D009456"}],"text":"Neuregulin-1 beta and neuregulin-1 alpha differentially affect the migration and invasion of malignant peripheral nerve sheath tumor cells.\nMalignant peripheral nerve sheath tumors (MPNSTs) are the most common malignancy associated with neurofibromatosis Type 1 (NF1). These Schwann cell lineage-derived sarcomas aggressively invade adjacent nerve and soft tissue, frequently precluding surgical resection. Little is known regarding the mechanisms underlying this invasive behavior. We have shown that MPNSTs express neuregulin-1 (NRG-1) beta isoforms, which promote Schwann cell migration during development, and NRG-1 alpha isoforms, whose effects on Schwann cells are poorly understood. Hypothesizing that NRG-1 beta and/or NRG-1 alpha promote MPNST invasion, we found that NRG-1 beta promoted MPNST migration in a substrate-specific manner, markedly enhancing migration on laminin but not on collagen type I or fibronectin. The NRG-1 receptors erbB3 and erbB4 were present in MPNST invadopodia (processes mediating invasion), partially colocalized with focal adhesion kinase and the laminin receptor beta(1)-integrin and coimmunoprecipitated with beta(1)-integrin. NRG-1 beta stimulated human and murine MPNST cell migration and invasion in a concentration-dependent manner in three-dimensional migration assays, acting as a chemotactic factor. Both baseline and NRG-1 beta-induced migration were erbB-dependent and required the action of MEK 1/2, SAPK/JNK, PI-3 kinase, Src family kinases and ROCK-I/II. In contrast, NRG-1 alpha had no effect on the migration and invasion of some MPNST lines and inhibited the migration of others. While NRG-1 beta potently and persistently activated Erk 1/2, SAPK/JNK, Akt and Src family kinases, NRG-1 alpha did not activate Akt and activated these other kinases with kinetics distinct from those evident in NRG-1 beta-stimulated cells. These findings suggest that NRG-1 beta enhances MPNST migration and that NRG-1 beta and NRG-1 alpha differentially modulate this process."}

{"project":"LitCoin-MONDO_bioort2019","denotations":[{"id":"T1","span":{"begin":93,"end":132},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T2","span":{"begin":140,"end":180},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T3","span":{"begin":182,"end":188},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T4","span":{"begin":210,"end":220},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T5","span":{"begin":237,"end":261},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T6","span":{"begin":263,"end":266},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T7","span":{"begin":304,"end":312},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T8","span":{"begin":502,"end":508},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T9","span":{"begin":747,"end":752},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T10","span":{"begin":797,"end":802},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T11","span":{"begin":980,"end":985},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T12","span":{"begin":1208,"end":1213},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T13","span":{"begin":1586,"end":1591},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T14","span":{"begin":1926,"end":1931},"obj":"DiseaseOrPhenotypicFeature"}],"attributes":[{"id":"A3","pred":"#label","subj":"T3","obj":"D018319"},{"id":"A6","pred":"#label","subj":"T6","obj":"D009456"},{"id":"A1","pred":"#label","subj":"T1","obj":"D018319"},{"id":"A5","pred":"#label","subj":"T5","obj":"D009456"},{"id":"A11","pred":"#label","subj":"T11","obj":"D018319"},{"id":"A8","pred":"#label","subj":"T8","obj":"D018319"},{"id":"A10","pred":"#label","subj":"T10","obj":"D018319"},{"id":"A4","pred":"#label","subj":"T4","obj":"D009369"},{"id":"A2","pred":"#label","subj":"T2","obj":"D018319"},{"id":"A7","pred":"#label","subj":"T7","obj":"D012509"},{"id":"A12","pred":"#label","subj":"T12","obj":"D018319"},{"id":"A14","pred":"#label","subj":"T14","obj":"D018319"},{"id":"A9","pred":"#label","subj":"T9","obj":"D018319"},{"id":"A13","pred":"#label","subj":"T13","obj":"D018319"}],"text":"Neuregulin-1 beta and neuregulin-1 alpha differentially affect the migration and invasion of malignant peripheral nerve sheath tumor cells.\nMalignant peripheral nerve sheath tumors (MPNSTs) are the most common malignancy associated with neurofibromatosis Type 1 (NF1). These Schwann cell lineage-derived sarcomas aggressively invade adjacent nerve and soft tissue, frequently precluding surgical resection. Little is known regarding the mechanisms underlying this invasive behavior. We have shown that MPNSTs express neuregulin-1 (NRG-1) beta isoforms, which promote Schwann cell migration during development, and NRG-1 alpha isoforms, whose effects on Schwann cells are poorly understood. Hypothesizing that NRG-1 beta and/or NRG-1 alpha promote MPNST invasion, we found that NRG-1 beta promoted MPNST migration in a substrate-specific manner, markedly enhancing migration on laminin but not on collagen type I or fibronectin. The NRG-1 receptors erbB3 and erbB4 were present in MPNST invadopodia (processes mediating invasion), partially colocalized with focal adhesion kinase and the laminin receptor beta(1)-integrin and coimmunoprecipitated with beta(1)-integrin. NRG-1 beta stimulated human and murine MPNST cell migration and invasion in a concentration-dependent manner in three-dimensional migration assays, acting as a chemotactic factor. Both baseline and NRG-1 beta-induced migration were erbB-dependent and required the action of MEK 1/2, SAPK/JNK, PI-3 kinase, Src family kinases and ROCK-I/II. In contrast, NRG-1 alpha had no effect on the migration and invasion of some MPNST lines and inhibited the migration of others. While NRG-1 beta potently and persistently activated Erk 1/2, SAPK/JNK, Akt and Src family kinases, NRG-1 alpha did not activate Akt and activated these other kinases with kinetics distinct from those evident in NRG-1 beta-stimulated cells. These findings suggest that NRG-1 beta enhances MPNST migration and that NRG-1 beta and NRG-1 alpha differentially modulate this process."}

{"project":"LitCoin-Chemical-MeSH-CHEBI","denotations":[{"id":"T1","span":{"begin":896,"end":904},"obj":"ChemicalEntity"},{"id":"T2","span":{"begin":915,"end":926},"obj":"ChemicalEntity"},{"id":"T3","span":{"begin":1329,"end":1347},"obj":"ChemicalEntity"},{"id":"T4","span":{"begin":1443,"end":1446},"obj":"ChemicalEntity"}],"attributes":[{"id":"A1","pred":"ID:","subj":"T1","obj":"http://purl.obolibrary.org/obo/CHEBI_3815"},{"id":"A2","pred":"ID:","subj":"T2","obj":"http://purl.obolibrary.org/obo/CHEBI_5058"},{"id":"A3","pred":"ID:","subj":"T3","obj":"D002630"},{"id":"A4","pred":"ID:","subj":"T4","obj":"http://purl.obolibrary.org/obo/CHEBI_28398"}],"text":"Neuregulin-1 beta and neuregulin-1 alpha differentially affect the migration and invasion of malignant peripheral nerve sheath tumor cells.\nMalignant peripheral nerve sheath tumors (MPNSTs) are the most common malignancy associated with neurofibromatosis Type 1 (NF1). These Schwann cell lineage-derived sarcomas aggressively invade adjacent nerve and soft tissue, frequently precluding surgical resection. Little is known regarding the mechanisms underlying this invasive behavior. We have shown that MPNSTs express neuregulin-1 (NRG-1) beta isoforms, which promote Schwann cell migration during development, and NRG-1 alpha isoforms, whose effects on Schwann cells are poorly understood. Hypothesizing that NRG-1 beta and/or NRG-1 alpha promote MPNST invasion, we found that NRG-1 beta promoted MPNST migration in a substrate-specific manner, markedly enhancing migration on laminin but not on collagen type I or fibronectin. The NRG-1 receptors erbB3 and erbB4 were present in MPNST invadopodia (processes mediating invasion), partially colocalized with focal adhesion kinase and the laminin receptor beta(1)-integrin and coimmunoprecipitated with beta(1)-integrin. NRG-1 beta stimulated human and murine MPNST cell migration and invasion in a concentration-dependent manner in three-dimensional migration assays, acting as a chemotactic factor. Both baseline and NRG-1 beta-induced migration were erbB-dependent and required the action of MEK 1/2, SAPK/JNK, PI-3 kinase, Src family kinases and ROCK-I/II. In contrast, NRG-1 alpha had no effect on the migration and invasion of some MPNST lines and inhibited the migration of others. While NRG-1 beta potently and persistently activated Erk 1/2, SAPK/JNK, Akt and Src family kinases, NRG-1 alpha did not activate Akt and activated these other kinases with kinetics distinct from those evident in NRG-1 beta-stimulated cells. These findings suggest that NRG-1 beta enhances MPNST migration and that NRG-1 beta and NRG-1 alpha differentially modulate this process."}

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These Schwann cell lineage-derived sarcomas aggressively invade adjacent nerve and soft tissue, frequently precluding surgical resection. Little is known regarding the mechanisms underlying this invasive behavior. We have shown that MPNSTs express neuregulin-1 (NRG-1) beta isoforms, which promote Schwann cell migration during development, and NRG-1 alpha isoforms, whose effects on Schwann cells are poorly understood. Hypothesizing that NRG-1 beta and/or NRG-1 alpha promote MPNST invasion, we found that NRG-1 beta promoted MPNST migration in a substrate-specific manner, markedly enhancing migration on laminin but not on collagen type I or fibronectin. The NRG-1 receptors erbB3 and erbB4 were present in MPNST invadopodia (processes mediating invasion), partially colocalized with focal adhesion kinase and the laminin receptor beta(1)-integrin and coimmunoprecipitated with beta(1)-integrin. 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