FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2958759871> ?p ?o ?g. }

• W2958759871 abstract "We have found that erbB receptor tyrosine kinases drive Ras hyperactivation and growth in NF1-null malignant peripheral nerve sheath tumors (MPNSTs). However, MPNSTs variably express multiple erbB receptors with distinct functional characteristics and it is not clear which of these receptors drive MPNST pathogenesis. Here, we test the hypothesis that altered erbB4 expression promotes MPNST pathogenesis by uniquely activating key cytoplasmic signaling cascades.ErbB4 expression was assessed using immunohistochemistry, immunocytochemistry, immunoblotting and real-time PCR. To define erbB4 functions, we generated mice that develop MPNSTs with floxed Erbb4 alleles (P0-GGFβ3;Trp53+/-;Erbb4flox/flox mice) and ablated Erbb4 in these tumors. MPNST cell proliferation and survival was assessed using 3H-thymidine incorporation, MTT assays, Real-Time Glo and cell count assays. Control and Erbb4-null MPNST cells were orthotopically xenografted in immunodeficient mice and the growth, proliferation (Ki67 labeling), apoptosis (TUNEL labeling) and angiogenesis of these grafts was analyzed. Antibody arrays querying cytoplasmic kinases were used to identify erbB4-responsive kinases. Pharmacologic or genetic inhibition was used to identify erbB4-responsive kinases that drive proliferation.Aberrant erbB4 expression was evident in 25/30 surgically resected human MPNSTs and in MPNSTs from genetically engineered mouse models (P0-GGFβ3 and P0-GGFβ3;Trp53+/- mice); multiple erbB4 splice variants that differ in their ability to activate PI3 kinase and nuclear signaling were present in MPNST-derived cell lines. Erbb4-null MPNST cells demonstrated decreased proliferation and survival and altered morphology relative to non-ablated controls. Orthotopic allografts of Erbb4-null cells were significantly smaller than controls, with reduced proliferation, survival and vascularization. ERBB4 knockdown in human MPNST cells similarly inhibited DNA synthesis and viability. Although we have previously shown that broad-spectrum erbB inhibitors inhibit Ras activation, Erbb4 ablation did not affect Ras activation, suggesting that erbB4 drives neoplasia via non-Ras dependent pathways. An analysis of 43 candidate kinases identified multiple NRG1β-responsive and erbB4-dependent signaling cascades including the PI3K, WNK1, STAT3, STAT5 and phospholipase-Cγ pathways. Although WNK1 inhibition did not alter proliferation, inhibition of STAT3, STAT5 and phospholipase-Cγ markedly reduced proliferation.ErbB4 promotes MPNST growth by activating key non-Ras dependent signaling cascades including the STAT3, STAT5 and phospholipase-Cγ pathways. ErbB4 and its effector pathways are thus potentially useful therapeutic targets in MPNSTs." @default.
• W2958759871 created "2019-07-23" @default.
• W2958759871 creator A5028814344 @default.
• W2958759871 creator A5033785127 @default.
• W2958759871 creator A5059291012 @default.
• W2958759871 creator A5067993987 @default.
• W2958759871 creator A5068853971 @default.
• W2958759871 creator A5071472484 @default.
• W2958759871 creator A5081724878 @default.
• W2958759871 date "2019-07-10" @default.
• W2958759871 modified "2023-10-17" @default.
• W2958759871 title "ErbB4 promotes malignant peripheral nerve sheath tumor pathogenesis via Ras-independent mechanisms" @default.
• W2958759871 cites W1853698148 @default.
• W2958759871 cites W1963585816 @default.
• W2958759871 cites W1965229389 @default.
• W2958759871 cites W1981108516 @default.
• W2958759871 cites W1987937498 @default.
• W2958759871 cites W2016010426 @default.
• W2958759871 cites W2018141976 @default.
• W2958759871 cites W2019797166 @default.
• W2958759871 cites W2022956052 @default.
• W2958759871 cites W2025029856 @default.
• W2958759871 cites W2026686051 @default.
• W2958759871 cites W2031047035 @default.
• W2958759871 cites W2031264513 @default.
• W2958759871 cites W2031892485 @default.
• W2958759871 cites W2032220244 @default.
• W2958759871 cites W2032969727 @default.
• W2958759871 cites W2034887388 @default.
• W2958759871 cites W2034955355 @default.
• W2958759871 cites W2037980730 @default.
• W2958759871 cites W2040742535 @default.
• W2958759871 cites W2053936821 @default.
• W2958759871 cites W2055024947 @default.
• W2958759871 cites W2055446870 @default.
• W2958759871 cites W2060362092 @default.
• W2958759871 cites W2063057728 @default.
• W2958759871 cites W2066104717 @default.
• W2958759871 cites W2070604281 @default.
• W2958759871 cites W2079681470 @default.
• W2958759871 cites W2088035322 @default.
• W2958759871 cites W2089776151 @default.
• W2958759871 cites W2089794529 @default.
• W2958759871 cites W2092544528 @default.
• W2958759871 cites W2104019822 @default.
• W2958759871 cites W2107398189 @default.
• W2958759871 cites W2109311831 @default.
• W2958759871 cites W2115632196 @default.
• W2958759871 cites W2119769850 @default.
• W2958759871 cites W2121136307 @default.
• W2958759871 cites W2131589269 @default.
• W2958759871 cites W2135198700 @default.
• W2958759871 cites W2139574983 @default.
• W2958759871 cites W2145344722 @default.
• W2958759871 cites W2149699507 @default.
• W2958759871 cites W2153862284 @default.
• W2958759871 cites W2155888371 @default.
• W2958759871 cites W2157310617 @default.
• W2958759871 cites W2275144157 @default.
• W2958759871 cites W2283735095 @default.
• W2958759871 cites W2320419876 @default.
• W2958759871 cites W2328039638 @default.
• W2958759871 cites W2404337602 @default.
• W2958759871 cites W2790714922 @default.
• W2958759871 cites W2900044275 @default.
• W2958759871 cites W4296759778 @default.
• W2958759871 doi "https://doi.org/10.1186/s12964-019-0388-5" @default.
• W2958759871 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6621970" @default.
• W2958759871 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31291965" @default.
• W2958759871 hasPublicationYear "2019" @default.
• W2958759871 type Work @default.
• W2958759871 sameAs 2958759871 @default.
• W2958759871 citedByCount "16" @default.
• W2958759871 countsByYear W29587598712019 @default.
• W2958759871 countsByYear W29587598712020 @default.
• W2958759871 countsByYear W29587598712021 @default.
• W2958759871 countsByYear W29587598712022 @default.
• W2958759871 countsByYear W29587598712023 @default.
• W2958759871 crossrefType "journal-article" @default.
• W2958759871 hasAuthorship W2958759871A5028814344 @default.
• W2958759871 hasAuthorship W2958759871A5033785127 @default.
• W2958759871 hasAuthorship W2958759871A5059291012 @default.
• W2958759871 hasAuthorship W2958759871A5067993987 @default.
• W2958759871 hasAuthorship W2958759871A5068853971 @default.
• W2958759871 hasAuthorship W2958759871A5071472484 @default.
• W2958759871 hasAuthorship W2958759871A5081724878 @default.
• W2958759871 hasBestOaLocation W29587598711 @default.
• W2958759871 hasConcept C101544691 @default.
• W2958759871 hasConcept C142724271 @default.
• W2958759871 hasConcept C184235292 @default.
• W2958759871 hasConcept C203014093 @default.
• W2958759871 hasConcept C2779251935 @default.
• W2958759871 hasConcept C2780942790 @default.
• W2958759871 hasConcept C2780943970 @default.
• W2958759871 hasConcept C502942594 @default.
• W2958759871 hasConcept C54355233 @default.
• W2958759871 hasConcept C62112901 @default.
• W2958759871 hasConcept C62478195 @default.
• W2958759871 hasConcept C71924100 @default.
• W2958759871 hasConcept C86803240 @default.

• next