{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1360004235487225600.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1111/cas.12115"}},{"identifier":{"@type":"URI","@value":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fcas.12115"}},{"identifier":{"@type":"URI","@value":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/cas.12115"}},{"identifier":{"@type":"PMID","@value":"23360421"}}],"resourceType":"学術雑誌論文(journal article)","dc:title":[{"@value":"Novel adaptor protein <scp>S</scp>hf interacts with <scp>ALK</scp> receptor and negatively regulates its downstream signals in neuroblastoma"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>Our neuroblastoma c<jats:styled-content style=\"fixed-case\">DNA</jats:styled-content> project previously identified <jats:italic><jats:styled-content style=\"fixed-case\">S</jats:styled-content></jats:italic>rc <jats:italic>h</jats:italic>omology 2 domain containing <jats:italic><jats:styled-content style=\"fixed-case\">F</jats:styled-content></jats:italic> (<jats:italic><jats:styled-content style=\"fixed-case\">S</jats:styled-content>hf</jats:italic>) as one of the genes expressed at high levels in favorable neuroblastoma. <jats:styled-content style=\"fixed-case\">S</jats:styled-content>hf is an adaptor protein containing four putative tyrosine phosphorylation sites and an <jats:styled-content style=\"fixed-case\">SH</jats:styled-content>2 domain. In this study, we found that <jats:styled-content style=\"fixed-case\">S</jats:styled-content>hf interacted with anaplastic lymphoma kinase (<jats:styled-content style=\"fixed-case\">ALK</jats:styled-content>), an oncogenic receptor tyrosine kinase in neuroblastoma. Real‐time <jats:styled-content style=\"fixed-case\">PCR</jats:styled-content> analysis showed that <jats:italic><jats:styled-content style=\"fixed-case\">S</jats:styled-content>hf</jats:italic> m<jats:styled-content style=\"fixed-case\">RNA</jats:styled-content> is highly expressed in non‐metastatic neuroblastomas compared to metastatic tumor samples (<jats:italic>P</jats:italic> < 0.030, <jats:italic>n</jats:italic> = 106). Interestingly, patients showing high <jats:italic><jats:styled-content style=\"fixed-case\">ALK</jats:styled-content></jats:italic> and low <jats:italic><jats:styled-content style=\"fixed-case\">S</jats:styled-content>hf</jats:italic> m<jats:styled-content style=\"fixed-case\">RNA</jats:styled-content> expressions showed poor prognosis, whereas low <jats:italic><jats:styled-content style=\"fixed-case\">ALK</jats:styled-content></jats:italic> and high <jats:italic><jats:styled-content style=\"fixed-case\">S</jats:styled-content>hf</jats:italic> expressions were related to better prognosis (<jats:italic>P</jats:italic> < 0.023, <jats:italic>n</jats:italic> = 38). Overexpression of <jats:styled-content style=\"fixed-case\">ALK</jats:styled-content> and si<jats:styled-content style=\"fixed-case\">RNA</jats:styled-content>‐mediated knockdown of <jats:italic><jats:styled-content style=\"fixed-case\">S</jats:styled-content>hf</jats:italic> yielded similar results, such as an increase in cellular growth and phosphorylation of <jats:styled-content style=\"fixed-case\">ALK</jats:styled-content>, in addition to <jats:styled-content style=\"fixed-case\">E</jats:styled-content>rk1/2 and signal transducer and activator of transcription 3 (STAT3) that are downstream signals of the <jats:styled-content style=\"fixed-case\">ALK</jats:styled-content>‐initiated phospho‐transduction pathway. Knockdown of <jats:italic><jats:styled-content style=\"fixed-case\">S</jats:styled-content>hf</jats:italic> also increased the cellular mobility and invasive capability of neuroblastoma cells. These results suggest that <jats:styled-content style=\"fixed-case\">S</jats:styled-content>hf interacts with <jats:styled-content style=\"fixed-case\">ALK</jats:styled-content> and negatively regulates the <jats:styled-content style=\"fixed-case\">ALK</jats:styled-content>‐initiated signal transduction pathway in neuroblastoma. We thus propose that <jats:styled-content style=\"fixed-case\">S</jats:styled-content>hf inhibits phospho‐transduction signals mediated by <jats:styled-content style=\"fixed-case\">ALK</jats:styled-content>, which is one of the major key players on neuroblastoma development, resulting in better prognosis of the tumor.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380004235487225601","@type":"Researcher","foaf:name":[{"@value":"Daisuke Takagi"}],"jpcoar:affiliationName":[{"@value":"Division of Biochemistry and Innovative Cancer Therapeutics Chiba Cancer Center Research Institute Chiba Japan"},{"@value":"Department of Oncology Immunology and Surgery Nagoya City University Graduate School of Medical Sciences Nagoya 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