{"created":"2024-02-29T02:48:59.915250+00:00","id":2000155,"links":{},"metadata":{"_buckets":{"deposit":"5fa2f3c6-55f8-4438-bcb4-9ceabfcdba6d"},"_deposit":{"created_by":29,"id":"2000155","owner":"18","owners":[29],"pid":{"revision_id":0,"type":"depid","value":"2000155"},"status":"published"},"_oai":{"id":"oai:ir.kagoshima-u.ac.jp:02000155","sets":["57:86"]},"author_link":["143931"],"item_5_date_6":{"attribute_name":"作成日","attribute_value_mlt":[{"subitem_date_issued_datetime":"2024-02-13","subitem_date_issued_type":"Collected"}]},"item_5_date_granted_54":{"attribute_name":"学位授与年月日 ","attribute_value_mlt":[{"subitem_dategranted":"2024-02-20"}]},"item_5_degree_grantor_53":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_language":"ja","subitem_degreegrantor_name":"鹿児島大学"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"17701","subitem_degreegrantor_identifier_scheme":"kakenhi"}]}]},"item_5_degree_name_42":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士(医学)","subitem_degreename_language":"ja"},{"subitem_degreename":"Doctor of Philosophy in Medical Science","subitem_degreename_language":"en"}]},"item_5_description_17":{"attribute_name":"ファイル（説明）","attribute_value_mlt":[{"subitem_description":"博士論文全文, 博士論文要旨, 最終試験結果の要旨, 論文審査の要旨","subitem_description_language":"ja","subitem_description_type":"Other"}]},"item_5_description_4":{"attribute_name":"要約(Abstract)","attribute_value_mlt":[{"subitem_description":"Multitargeted receptor tyrosine kinase inhibitors, including vascular endothelial growth factor (VEGF) inhibitors, such as sunitinib, have been used as the primary targeted agents for patients with recurrent or distant metastasis of advanced renal cell carcinoma (RCC). However, endogenous or acquired sunitinib resistance has become a significant therapeutic problem. Therefore, we focused on mechanisms of sunitinib resistance in RCC. First, we undertook RNA sequencing analysis using previously established sunitinib-resistant RCC (SUR-Caki1, SUR-ACHN, and SUR-A498) cells. The results showed increased expression of secretogranin II (SCG2, chromogranin C) in SUR-RCC cells compared to parental cells. The Cancer Genome Atlas database showed that SCG2 expression was increased in RCC compared to normal renal cells. In addition, the survival rate of the SCG2 high-expression group was significantly lower than that of the RCC low-expression group. Thus, we investigated the involvement of SCG2 in sunitinib-resistant RCC. In vitro analysis showed that migratory and invasive abilities were suppressed by SCG2 knockdown SUR cells. As SCG2 was previously reported to be associated with angiogenesis, we undertook a tube formation assay. The results showed that suppression of SCG2 inhibited angiogenesis. Furthermore, coimmunoprecipitation assays revealed a direct interaction between SCG2 and hypoxia-inducible factor 1α (HIF1α). Expression levels of VEGF-A and VEGF-C downstream of HIF1α were found to be decreased in SCG2 knockdown SUR cells. In conclusion, SCG2 could be associated with sunitinib resistance through VEGF regulation in RCC cells. These findings could lead to a better understanding of the VHL/HIF/VEGF pathway and the development of new therapeutic strategies for sunitinib-resistant RCC.","subitem_description_language":"en","subitem_description_type":"Other"},{"subitem_description":"Wataru Fukumoto, Hirofumi Yoshino, Shin-Ichi Horike, Issei Kawakami, Motoki Tamai, Junya Arima, Ichiro Kawahara, Akihiko Mitsuke, Takashi Sakaguchi, Satoru Inoguchi, Makiko Meguro-Horike, Shuichi Tatarano, Hideki Enokida\nPotential therapeutic target secretogranin II might cooperate with hypoxia-inducible factor 1α in sunitinib-resistant renal cell carcinoma\nCancer Science. 2023;00:1–11.\nhttps://doi.org/10.1111/cas.15914","subitem_description_language":"en","subitem_description_type":"Other"}]},"item_5_dissertation_number_55":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲総研第724号"}]},"item_5_publisher_23":{"attribute_name":"公開者・出版者","attribute_value_mlt":[{"subitem_publisher":"鹿児島大学","subitem_publisher_language":"ja"},{"subitem_publisher":"John Wiley & Sons","subitem_publisher_language":"en"}]},"item_5_text_44":{"attribute_name":"備考","attribute_value_mlt":[{"subitem_text_language":"ja","subitem_text_value":"【指導教員:榎田英樹】"}]},"item_5_text_47":{"attribute_name":"date.appl","attribute_value_mlt":[{"subitem_text_value":"【学位申請日】2023-09-06"}]},"item_5_version_type_14":{"attribute_name":"著者版フラグ","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":"福元, 渉","creatorNameLang":"ja"},{"creatorName":"フクモト, ワタル","creatorNameLang":"ja-Kana"},{"creatorName":"Fukumoto, Wataru","creatorNameLang":"en"}],"familyNames":[{"familyName":"福元","familyNameLang":"ja"},{"familyName":"フクモト","familyNameLang":"ja-Kana"},{"familyName":"Fukumoto","familyNameLang":"en"}],"givenNames":[{"givenName":"渉","givenNameLang":"ja"},{"givenName":"ワタル","givenNameLang":"ja-Kana"},{"givenName":"Wataru","givenNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"143931","nameIdentifierScheme":"WEKO"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_access","date":[{"dateType":"Available","dateValue":"2025-07-02"}],"displaytype":"detail","fileDate":[{"fileDateType":"Collected","fileDateValue":"2024-02-13"}],"filename":"Diss_FUKUMOTO_Wataru_ISK724_2024.pdf","filesize":[{"value":"2.0 MB"}],"format":"application/pdf","licensetype":"license_3","mimetype":"application/pdf","url":{"label":"Diss_FUKUMOTO_Wataru_ISK724_2024.pdf","objectType":"fulltext","url":"https://ir.kagoshima-u.ac.jp/record/2000155/files/Diss_FUKUMOTO_Wataru_ISK724_2024.pdf"},"version_id":"2d857567-3a5a-4c17-953e-3405f8f131da"},{"accessrole":"open_access","date":[{"dateType":"Available","dateValue":"2025-07-02"}],"displaytype":"detail","fileDate":[{"fileDateType":"Collected","fileDateValue":"2024-02-13"}],"filename":"Abstract_FUKUMOTO_Wataru_4519810310_2023.pdf","filesize":[{"value":"74.2 KB"}],"format":"application/pdf","mimetype":"application/pdf","url":{"label":"Abstract_FUKUMOTO_Wataru_4519810310_2023.pdf","objectType":"abstract","url":"https://ir.kagoshima-u.ac.jp/record/2000155/files/Abstract_FUKUMOTO_Wataru_4519810310_2023.pdf"},"version_id":"063fbef2-3c0f-4cae-91bd-0c60eef9b3c5"},{"accessrole":"open_access","date":[{"dateType":"Available","dateValue":"2024-02-29"}],"displaytype":"detail","fileDate":[{"fileDateType":"Collected","fileDateValue":"2024-02-13"}],"filename":"Result_FUKUMOTO_Wataru _isk_724.pdf","filesize":[{"value":"125 KB"}],"format":"application/pdf","mimetype":"application/pdf","url":{"label":"Result_FUKUMOTO_Wataru _isk_724.pdf","objectType":"other","url":"https://ir.kagoshima-u.ac.jp/record/2000155/files/Result_FUKUMOTO_Wataru _isk_724.pdf"},"version_id":"85f7a42c-c746-4762-97bb-be3925d066bb"},{"accessrole":"open_access","date":[{"dateType":"Available","dateValue":"2024-02-29"}],"displaytype":"detail","fileDate":[{"fileDateType":"Collected","fileDateValue":"2024-02-13"}],"filename":"Comments_FUKUMOTO_Wataru _isk_724.pdf","filesize":[{"value":"50 KB"}],"format":"application/pdf","mimetype":"application/pdf","url":{"label":"Comments_FUKUMOTO_Wataru _isk_724.pdf","objectType":"other","url":"https://ir.kagoshima-u.ac.jp/record/2000155/files/Comments_FUKUMOTO_Wataru _isk_724.pdf"},"version_id":"eeebdd56-f9e7-4a85-a940-73ea21e289c0"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"angiogenesis","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"HIF1α","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"renal cell carcinoma","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"SCG2","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"sunitinib resistance","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"},{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"doctoral thesis","resourceuri":"http://purl.org/coar/resource_type/c_db06"}]},"item_title":"Potential therapeutic target secretogranln II might cooperate with hypoxia-inducible factor 1α in sunitinib-resistant renal cell carcinoma","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Potential therapeutic target secretogranln II might cooperate with hypoxia-inducible factor 1α in sunitinib-resistant renal cell carcinoma","subitem_title_language":"en"},{"subitem_title":"潜在的な治療標的SCG2は、スニチニブ耐性腎細胞癌においてHIF1αと連携する可能性がある","subitem_title_language":"ja"}]},"item_type_id":"5","owner":"29","path":["86"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2024-02-29"},"publish_date":"2024-02-29","publish_status":"0","recid":"2000155","relation_version_is_last":true,"title":["Potential therapeutic target secretogranln II might cooperate with hypoxia-inducible factor 1α in sunitinib-resistant renal cell carcinoma"],"weko_creator_id":"29","weko_shared_id":-1},"updated":"2025-07-02T00:21:56.121388+00:00"}