{"created":"2025-01-24T00:31:47.360426+00:00","id":2000301,"links":{},"metadata":{"_buckets":{"deposit":"9826cd41-9479-4dc7-a235-79f8a86187c0"},"_deposit":{"created_by":3,"id":"2000301","owner":"3","owners":[3],"pid":{"revision_id":0,"type":"depid","value":"2000301"},"status":"published"},"_oai":{"id":"oai:asahikawa-med.repo.nii.ac.jp:02000301","sets":["7:27:45"]},"author_link":[],"control_number":"2000301","item_10_alternative_title_3":{"attribute_name":"その他（別言語等）のタイトル","attribute_value_mlt":[{"subitem_alternative_title":"GNAS変異はKRAS経路に拮抗することにより、膵癌の悪性度を抑える","subitem_alternative_title_language":"ja"}]},"item_10_biblio_info_21":{"attribute_name":"bibliographic_information","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2022-05-01","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"3","bibliographicPageEnd":"220","bibliographicPageStart":"208","bibliographicVolumeNumber":"57","bibliographic_titles":[{"bibliographic_title":"Journal of gastroenterology","bibliographic_titleLang":"en"}]}]},"item_10_date_granted_30":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2022-06-30"}]},"item_10_degree_grantor_32":{"attribute_name":"item_10_degree_grantor_32","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_language":"ja","subitem_degreegrantor_name":"旭川医科大学"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"10107","subitem_degreegrantor_identifier_scheme":"kakenhi"}]}]},"item_10_degree_name_31":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士（医学）","subitem_degreename_language":"ja"}]},"item_10_description_28":{"attribute_name":"識別番号 その他","attribute_value_mlt":[{"subitem_description":"PMID:35018527","subitem_description_language":"en","subitem_description_type":"Other"}]},"item_10_description_33":{"attribute_name":"item_10_description_33","attribute_value_mlt":[{"subitem_description":"Background: Mutations in GNAS drive pancreatic tumorigenesis and frequently occur in intraductal papillary mucinous neoplasm (IPMN); however, their value as a therapeutic target is yet to be determined. This study aimed at evaluating the involvement of mutant GNAS in tumor aggressiveness in established pancreatic cancer.\n\nMethods: CRISPR/Cas9-mediated GNAS R201H silencing was performed using human primary IPMN-associated pancreatic cancer cells. The role of oncogenic GNAS in tumor maintenance was evaluated by conducting cell culture and xenograft experiments, and western blotting and transcriptome analyses were performed to uncover GNAS-driven signatures.\n\nResults: Xenografts of GNAS wild-type cells were characterized by a higher Ki-67 labeling index relative to GNAS-mutant cells. Phenotypic alterations in the GNAS wild-type tumors resulted in a significant reduction in mucin production accompanied by solid with massive stromal components. Transcriptional profiling suggested an apparent conflict of mutant GNAS with KRAS signaling. A significantly higher Notch intercellular domain (NICD) was observed in the nuclear fraction of GNAS wild-type cells. Meanwhile, inhibition of protein kinase A (PKA) induced NICD in GNAS-mutant IPMN cells, suggesting that NOTCH signaling is negatively regulated by the GNAS-PKA pathway. GNAS wild-type cells were characterized by a significant invasive property relative to GNAS-mutant cells, which was mediated through the NOTCH regulatory pathway.\n\nConclusions: Oncogenic GNAS induces mucin production, not only via MUC2 but also via MUC5AC/B, which may enlarge cystic lesions in the pancreas. The mutation may also limit tumor aggressiveness by attenuating NOTCH signaling; therefore, such tumor-suppressing effects must be considered when therapeutically inhibiting the GNAS pathway.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_10_dissertation_number_29":{"attribute_name":"dissertation_number","attribute_value_mlt":[{"subitem_dissertationnumber":"甲第578号"}]},"item_10_relation_24":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type":"isIdenticalTo","subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.1007/s00535-021-01846-4","subitem_relation_type_select":"DOI"}}]},"item_10_source_id_22":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"0944-1174","subitem_source_identifier_type":"PISSN"}]},"item_10_version_type_38":{"attribute_name":"出版タイプ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_abf2"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"河端, 秀賢","creatorNameLang":"ja","creatorNameType":"Personal"},{"creatorName":"カワバタ, ヒデマサ","creatorNameLang":"ja-Kana","creatorNameType":"Personal"},{"creatorName":"Kawabata, Hidemasa","creatorNameLang":"en","creatorNameType":"Personal"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_access","date":[{"dateType":"Available","dateValue":"2025-01-24"}],"filename":"K578 Kawabata Hidemasa_TD.pdf","filesize":[{"value":"1.7 MB"}],"format":"application/pdf","mimetype":"application/pdf","url":{"objectType":"fulltext","url":"https://asahikawa-med.repo.nii.ac.jp/record/2000301/files/K578 Kawabata Hidemasa_TD.pdf"},"version_id":"bf75dd83-3ff9-44bf-ad28-fec285ad4ad2"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"GNAS","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Intraductal papillary mucinous neoplasm","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"NOTCH","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Primary culture","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"item_resource_type","attribute_value_mlt":[{"resourcetype":"doctoral thesis","resourceuri":"http://purl.org/coar/resource_type/c_db06"}]},"item_title":"Mutant GNAS limits tumor aggressiveness in established pancreatic cancer via antagonizing the KRAS-pathway","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Mutant GNAS limits tumor aggressiveness in established pancreatic cancer via antagonizing the KRAS-pathway","subitem_title_language":"en"}]},"item_type_id":"10","owner":"3","path":["45"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2022-09-07"},"publish_date":"2022-09-07","publish_status":"0","recid":"2000301","relation_version_is_last":true,"title":["Mutant GNAS limits tumor aggressiveness in established pancreatic cancer via antagonizing the KRAS-pathway"],"weko_creator_id":"3","weko_shared_id":-1},"updated":"2025-01-24T00:54:04.921069+00:00"}